Eggplant is a species of S. melongena, belonging to the family Solanaceae and native to India. The plant has been cultivated in southern and eastern Asia since prehistory. It is famous with its deeply purple and the best eggplant can be found from August through October when it is in season.
Nutritional Supplements
1. Carbohydrates
2. Sugars
3. Fiber
4. Fat
5. Protein
6. Thiamine (Vitamin B1)
7. Riboflavin (Vitamin B2)
8. Niacin (Vitamin B3)
9. Pantothenic acid (B5)
10. Vitamin B6
11. Folate (Vitamin B9)
12. Vitamin C
13. Tryptophan
14. Manganese
15. Calcium
16. Copper
17. Iron
18. Magnesium
19. Phosphorus
20. Potassium
21. Zinc
22. Etc.
Chemical constituents
The vegetable chemical compounds containing include sterols (i.e. typical plant sterols, androstane, pregnane and cholestane derivatives, steroidal alkaloids and sapogenins), phytosterols, triterpenes, δ-amyrin, Chlorogenic acid, Nasunin and other Polyphenolic compounds.
1. Eggplant and cancer
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.
The study of antiproliferative activities against human colon (HT29) and liver (HepG2) cancer cells conducted by Yeungnam University, the eggplant glycoalkaloids solamargine showed to inhibit both cancer cell lines but greater in colon cancer cell line(1). In human fibrosarcoma HT-1080 cell, delphinidin, a flavonoid pigment contained in the peel of eggplant, slightly inhibited tumor cell invasiveness probably through slight inhibition of the activity of MMPs(secretes matrix metalloproteinase)(2). According to Dr. Shimada A. in an one year (continuous 2 days for 12 months) food surveys held at 5 areas in Japan, the frequency of intake eggplant may associate to increase risk of gastric cancer and gastric cancer mortality rate(3), but may account partly for the geographic variation in gastric cancer mortality in Japan(4).
References
(1) Glycoalkaloids and metabolites inhibit the growth of human colon (HT29) and liver (HepG2) cancer cells by Lee KR1, Kozukue N, Han JS, Park JH, Chang EY, Baek EJ, Chang JS, Friedman M.(PubMed)
(2) Inhibitory effect of delphinidin from Solanum melongena on human fibrosarcoma HT-1080 invasiveness in vitro by Nagase H1, Sasaki K, Kito H, Haga A, Sato T.(PubMed)
(3) [Regional differences in gastric cancer mortality and eating habits of people].[Article in Japanese] by Shimada A.(PubMed)
(4) Food consumption and gastric cancer mortality in five regions of Japan by Tsubono Y1, Kobayashi M, Tsugane S.(PubMed)
2. Eggplant and cholesterol
Cholesterol is needed for our body to build cell walls, make hormones and vitamin D, and create bile salts that help you digest fat. However too much of it can be dangerous because cholesterol cannot dissolve in your blood. The special particle called lipoprotein moves this waxy, soft substance from place to place. If you have too much low density lipoprotein LDL that is known as bad cholesterol, overtime cholesterol can build up in your arterial walls causing blockage and leading to heart attack and stroke.
Eggplant (Solanum melongena) has been used as hypocholesterolemic agent in many countries, including Brazil. its phenolic may has the potential to reduce hyperglycemia-induced pathogenesis linked to cellular oxidation stress(1). In a study of 38 hypercholesterolemic human volunteers ingesting S. melongena infusion for five weeks, researchers found no differences when compared to control, but in Intraindividual analysis S. melongena infusion significantly reduced the blood levels of total and LDL cholesterol and of apolipoprotein B(1).
But in a double-blind placebo-controlled study of the effectiveness of oral Solanum melongena (SM) against hyperlipidemia, showed the potential result in decreased serum total cholesterol, LDL-c and LDL-c/HDL-c, but no change in serum triglycerides, HDL-c, VLDL-c, AST, ALT, gGT, glucose and body mass index, after 3 months(2) and according to Universidade Federal de Minas Gerais, eggplant did not alter the total cholesterol and atherogenic lipoproteins after 12 week of intake in its study (3).
References
(1) In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension by Kwon YI1, Apostolidis E, Shetty K.(PubMed)(2) Eggplant (Solanum melongena) infusion has a modest and transitory effect on hypercholesterolemic subjects by Guimarães PR1, Galvão AM, Batista CM, Azevedo GS, Oliveira RD, Lamounier RP, Freire N, Barros AM, Sakurai E, Oliveira JP, Vieira EC, Alvarez-Leite JI.(PubMed)(3) [Absence of hypolipidemic effect of Solanum melongena L. (eggplant) on hyperlipidemic patients].[Article in Portuguese] by Silva GE1, Takahashi MH, Eik Filho W, Albino CC, Tasim GE, Serri Lde A, Assef AH, Cortez DA, Bazotte RB.(PubMed)
(4) Effects of eggplant (Solanum melongena) on the atherogenesis and oxidative stress in LDL receptor knock out mice (LDLR(-/-)) by Botelho FV1, Enéas LR, Cesar GC, Bizzotto CS, Tavares E, Oliveira FA, Gloria MB, Silvestre MP, Arantes RM, Alvarez-Leite JI.(PubMed)
3. Eggplant as antioxidant
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
Eggplant fruit contains a rich source of polyphenol compounds endowed with antioxidant properties. According to Università degli Studi di Catania, dry peeled skin combined with 50% aqueous ethanol, irradiated with microwave contained showed a high quantity of flavonoids with good antioxidant activity expressed through its capacity to scavenge superoxide anion and to inhibit lipid peroxidation(1). Solanum anguivi fruit (SAG) exhibited potent and concentration dependent free radical-scavenging activity as well as protected against Ca(2+) (110 μmol/L)-induced mitochondrial swelling and maintained the mitochondrial membrane potential, in the evaluation of the antioxidant and radical scavenging activities of Solanum anguivi fruit (SAG) and its possible effect on mitochondrial permeability transition pore(2).
The City University of New York, in the study of the antioxidant-caffeoylquinic acid isomers in fruits of wild eggplant relatives, 3-O-malonyl-5-O-(E)-caffeoylquinic acid (isomer 1) and 4-O-(E)-caffeoyl-5-O-malonylquinic acid (isomer 2) exhibited free radical scavenging activity, albeit about 4-fold lower than that of the flavonol quercetin dehydrate(3).
References
(1) Antioxidant activity and phenolic content of microwave-assisted Solanum melongena extracts by Salerno L, Modica MN, Pittalà V, Romeo G, Siracusa MA, Di Giacomo C, Sorrenti V, Acquaviva R.(PubMed)
(2) African eggplant (Solanum anguivi Lam.) fruit with bioactive polyphenolic compounds exerts in vitro antioxidant properties and inhibits Ca(2+)-induced mitochondrial swelling by Elekofehinti OO1, Kamdem JP, Bolingon AA, Athayde ML, Lopes SR, Waczuk EP, Kade IJ, Adanlawo IG, Rocha JB.(PubMed)
(3) Two new antioxidant malonated caffeoylquinic acid isomers in fruits of wild eggplant relatives by Ma C1, Dastmalchi K, Whitaker BD, Kennelly EJ.(PubMed)
4. Eggplant and cardiovascular diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.
Animals fed freeze-dried products of either raw or grilled eggplants for 30 days study showed a positive effect of raw and cooked eggplant (Solanum melongena L) in increase left ventricular function, and reduce myocardial infarct size and cardiomyocyte apoptosis with high potency in grilled eggplants(1). According to Tuskegee University, eggplant containing high sources of phenolic compounds, which might provide anti-oxidative protection against free radicals in the human body and might reduce the risk of chronic diseases(2)
References
(1) Cardioprotective properties of raw and cooked eggplant (Solanum melongena L) by Das S1, Raychaudhuri U, Falchi M, Bertelli A, Braga PC, Das DK.(PubMed)
(2) Total phenolics and antioxidant capacity of indigenous vegetables in the southeast United States: Alabama Collaboration for Cardiovascular Equality Project by Huang Z1, Wang B, Eaves DH, Shikany JM, Pace RD.(PubMed)
5. Eggplant and Type II diabetes
Diabetes is defined as a condition caused by insufficient insulin entering the bloodstream to regulate the glucose. It is either caused by cells in pancreas dying off or receptor sites clogged up by fat and cholesterol. In some cases, diabetes is also caused by allergic reactions of cells in the immune system.
According to University of Massachusetts, phenolic-enriched extracts of eggplant with moderate free radical scavenging-linked antioxidant activity had high alpha-glucosidase inhibitory activity, through inhibition of key enzymes relevant for type 2 diabetes and hypertension(1). Chlorogenic acids (CGAs (71 compounds), being esters of derivatives of cinnamic acids with quinic acid found in many foods, including eggplant may be associated to reduce risk of the risk of human chronic diseases such as inflammation, diabetes(2).
References
(1) In vitro studies of eggplant (Solanum melongena) phenolics as inhibitors of key enzymes relevant for type 2 diabetes and hypertension by Kwon YI1, Apostolidis E, Shetty K.(PubMed)
(2) n outlook on chlorogenic acids-occurrence, chemistry, technology, and biological activities by Upadhyay R1, Mohan Rao LJ.(PubMed)
Wednesday, May 28, 2014
Monday, May 26, 2014
Phytochemicals Dithiolthiones (isothiocyanates)
Dithiolthiones are phytochemicals in the class of Organosulfides, found abundantly in cruciferous vegetables, garden sorrel, horseradish, etc.
The study of the hepatoprotective drug anisyldithiolthione was showed to be effective in acting as hepoprotective agent in inhibited lipid peroxidation induced in rat liver microsomes either chemically by FeSO4 and reducing agents (cysteine or ascorbate) or enzymatically, probably through the presence of its dithiolthione function(1) Other medication such as Anethol dithiolthione (ADT), usually prescribed as a choleretic drug, also exhibited an hepatoprotective potency at doses as low as 10 mg/kg relative to serum aminotransferase activities and hepatic glutathione related enzyme system in in Swiss female mice(2)
References
(1) A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione by Mansuy D, Sassi A, Dansette PM, Plat M.(PubMed)
(2) Protective effect of anethol dithiolthione against acetaminophen hepatotoxicity in mice by Warnet JM1, Christen MO, Thevenin M, Biard D, Jacqueson A, Claude JR.(PubMed).
2. Isothiocyanates and cancers
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.
In a case-control study conducted in urban Shanghai. The cases (from December 2006 to December 2008, ITC consumption from cruciferous vegetables intake showed a positive effect in reduce risk of pancreatic cancer after adjusting for possible confounding factors such as age, sex, history of diabetes and pancreatitis(1). Thiazolo, the synthesis of a novel class of quinazoline, produced by the reaction of 4,6-dichloro-5-aminopyrimidine with isothiocyanates in presence of 20 mol% KF/alumina, showed to exhibit antiproliferative activity in lung (NCI-H322 and A549), epidermal (A431) and glioblastoma (T98G), HL-60 cell lines at 20 μM. The effect of compound 4a on mitochondrial potential loss in HL-60 cells probably through cleavage of PARP-1 and procaspase-3 inhibition(2).
The study by Campus Morro do Cruzeiro suggested that the phytochemical inhibited the cell viability of human cervical cancer cells, human pancreatic cancer cells, human hepatocellular carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties in the treatment of human T-cell leukemia cells(3).
References
(1) [A case-control study on the association between urinary levels of isothiocyanates and the risk of pancreatic cancer].[Article in Chinese] by Wang J1, Han L, Zhang W, Wang J, Ni Q, Shen M, Gao Y2.(PubMed)
(2) Synthesis, antiproliferative and apoptosis-inducing activity of thiazolo[5,4-d]pyrimidines by Singh B1, Guru SK, Kour S, Jain SK, Sharma R, Sharma PR, Singh SK, Bhushan S, Bharate SB, Vishwakarma RA.(PubMed)
(3) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
3. Isothiocyanates as Antioxidants
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
In Fuchs endothelial corneal dystrophy (FECD), an oxidative stress disorder, treatment with Sulforaphane, a molecule within the isothiocyanate group, decreased CEC apoptosis by 55% in unstressed group and by 43% in tBHP-treated specimens, through inhibition of oxidative stress(1).
The Universidade Federal de Ouro Preto study also indicated the similar result of sulforaphane in improvement of antioxidant status in the testing of number of cancer cell lines(2). Other study suggested that isothiocyanates (ITCs), found abundantly in cruciferous vegetables, may be effective as a cancer chemopreventive agent through modulation of phase II detoxifying/antioxidant enzyme activities(3).
Reference
(1) Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy: a novel treatment by Ziaei A1, Schmedt T, Chen Y, Jurkunas UV.(PubMed)
(2) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
(3) Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression by Prawan A1, Keum YS, Khor TO, Yu S, Nair S, Li W, Hu L, Kong AN.(PubMed)
4. Isothiocyanates and heart diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.
There are many causes of heart diseases. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.
In human immunodeficiency virus (HIV) patients, showed to improve AIDS-related heart dysfunction through inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.(1). In ischemic injury of hearts patients, showed to inhibit reactive oxygen species mediators in exerting a toxic effect during ischemia-reperfusion through mitochondrial K(ATP) channels and antioxidant pathway(2). On ischaemia-reperfusion-induced cardiac injury. steamed broccoli showed a superior cardioprotective properties over cooked broccoli, probably through through the redox signalling of sulphoraphane(3). the phytochemical also found to trduce risk of vascular disease due to aging by inhibiting oxidative stress (4).
References
(1) Isothiocyanates ameliorate the symptom of heart dysfunction and mortality in a murine AIDS model by inhibiting apoptosis in the left ventricle. by Ho JN1, Yoon HG, Park CS, Kim S, Jun W, Choue R, Lee J.(PubMed)
(2) Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.by Piao CS1, Gao S, Lee GH, Kim do S, Park BH, Chae SW, Chae HJ, Kim SH.(PubMed)
(3) Comparison of the protective effects of steamed and cooked broccolis on ischaemia-reperfusion-induced cardiac injury. by Mukherjee S1, Lekli I, Ray D, Gangopadhyay H, Raychaudhuri U, Das DK.(PubMed)
(4) Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging by Chapple SJ1, Siow RC, Mann GE.(PubMed)
5. Isothiocyanates and neuroprotective effect
Sulforaphane, a naturally organosulfur compound found in broccoli, showed to exert its neuroprotective effects through significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex(1). in a variety of acute and chronic neurodegenerative diseases, phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, demonstrated its neuroprotective effects in several in vitro and in vivo studies, may be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway(2). In dopaminergic neurotoxicity in mice induced by 6-hydroxydopamine (6-OHDA), the phytochemical showed the neuroprotective effect through its ability to enhance glutathione levels and its dependent enzymes (glutathione-S-transferase and glutathione reductase) and to modulate neuronal survival pathways(3).
References
(1) Sulforaphane alleviates scopolamine-induced memory impairment in mice by Lee S1, Kim J1, Seo SG2, Choi BR3, Han JS3, Lee KW4, Kim J5.(PubMed)
(2) Sulforaphane as a potential protective phytochemical against neurodegenerative diseases byTarozzi A1, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P.(PubMed)
(3) Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease byMorroni F1, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P.(PubMed)
6. Sulforaphane and Obesity
Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.
Taking foods containing sulforaphane may be effective in managing weight loss for obese patients accompanied with change of lifestyle with more vegetables and fruits into diet. Sulforaphane, a molecule within the isothiocyanate group, according to Chungbuk National University, showed to prevent high-fat diet (HFD)-induced obesity in C57BL/6N mice. through inhibiting adipogenesis( the cells differentiation for a vital role in energy homeostasis and process the largest energy reserve in the body of animals). via down-regulation of PPARγ(regulation of metabolism) and C/EBPα (inflammatory process) and by suppressing lipogenesis( protein as an intermediate stage in metabolism of simple sugars) through activation of the AMPK(in cellular energy homeostasis) pathway(1). Chronic oral administration of sulforaphane, on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats, at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression involed neuronal glucose transport in the cerebral cortex and hypothalamus(2). The Chonbuk National University also suggested that Sulforaphane suppressed AMPK phosphorylation(cellular energy homeostasis) at Thr-172 in a dose-dependent manner(3).
References
(1) Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice by Choi KM1, Lee YS1, Kim W1, Kim SJ2, Shin KO1, Yu JY3, Lee MK1, Lee YM1, Hong JT1, Yun YP1, Yoo HS4.(PubMed)(2) Chronic sulforaphane oral treatment accentuates blood glucose impairment and may affect GLUT3 expression in the cerebral cortex and hypothalamus of rats fed with a highly palatable diet by Souza CG1, Riboldi BP, Hansen F, Moreira JD, Souza DG, de Assis AM, Brum LM, Perry ML, Souza DO.(PubMed)
(3) Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway by Lee JH1, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY.(PubMed)
7. Sulforaphane and Lung diseases
Lung diseases is defined as a condition, affecting the upper respiratory tract, trachea, bronchi, bronchioles, alveoli, pleura and pleural cavity, and the nerves and muscles of breathing.
Sulforaphane may be used as a preventive chemical constituent of pulmonary damage for patient who exposure to arsenic. According to China Medical University, arsenic-containing dust resulted in ; all of which were blocked by sulforaphane (SF) blocked pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung caused by 2 weeks of exposure to arsenic through activation of Nrf2(master regulator of the total antioxidant system)(1). In wildtype neonatal mice exposed to hyperoxia. SF also found to activated Nrf2 activation through induced expression of anti-oxidant genes,(2). In the lungs of the arrhythmic Clock(Δ19) mice, SF also activated it anti ovidative damage effect through activation of NRF2/glutathione defense pathway in combating oxidative/fibrotic lung damage(3).
References
(1) Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response. by Zheng Y1, Tao S, Lian F, Chau BT, Chen J, Sun G, Fang D, Lantz RC, Zhang DD.(PubMed)
(2) Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status by McGrath-Morrow SA1, Lauer T, Collaco JM, Lopez A, Malhotra D, Alekseyev YO, Neptune E, Wise R, Biswal S.(PubMed)
(3) The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis by Pekovic-Vaughan V1, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GT, Fukada Y, Meng QJ.(PubMed)
8. Sulforaphane and Liver disease
Liver disease in most cases are linked to alcohol or drugs. In fact, it can be caused by a variety of factors and affecting everyone from infants to older adults.
In CYP2E1-dependent binge alcohol-induced liver steatosis, oral treatment of sulforphane sulforaphane showed to activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels(1). In the comparison of the effectiveness of Sulforaphane and glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells, Dr Abdull Razis AF1, and Noor NM found that sulforphane is superior to glucoraphanin in modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro(2). The University of Rhode Island, Kingston study also insisted that SF activate Nrf2 activation in inhibited lipid accumulation in white adipose tissue, suppressed adipogenesis, induced insulin resistance and glucose intolerance, and increased hepatic steatosis in Lep(ob/ob) mice(3)..
References
(1) Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis by Zhou R1, Lin J, Wu D.(PubMed)
(2) Sulforaphane is superior to glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells by Abdull Razis AF1, Noor NM.(PubMed)
(3) Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice by Xu J1, Kulkarni SR, Donepudi AC, More VR, Slitt AL.(PubMed)
9. Sulforaphane and Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The University of Michigan, also insisted that ingestion of sulforaphane at a dose of 50 mg/kg for 2 weeks inhibited breast cancer stem cells(1). According to Manipal University, Sulforaphane inhibited growth of human breast cancer cell line MCF-7 cells, through induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 (anti-apoptotic protein) and COX-2 (inlvoved inflammatory process) respectively(2). Also in testing of MCF-7 breast cancer cells, researchers at the The Catholic University of Korea, showed that sulforaphane induced the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression(involved in keratinocyte migration and granulation tissue remodeling during wound healing) and cell invasion by via the suppression of the NF-κB (nvolved in cellular responses)pathway in MCF-7 cells(3).
References
(1) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells by Li Y1, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D.(PubMed)
(2) Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine by Hussain A1, Mohsin J, Prabhu SA, Begum S, Nusri Qel-A, Harish G, Javed E, Khan MA, Sharma C.(PubMed)
(3) Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells by Lee YR1, Noh EM, Han JH, Kim JM, Hwang BM, Kim BS, Lee SH, Jung SH, Youn HJ, Chung EY, Kim JS.(PubMed)
10. Sulforaphane and Prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams.
Oral administration of d,l-sulforaphane (SFN) can decrease the incidence or burden of early-stage prostate cancer [prostatic intraepithelial neoplasia (PIN)] and well-differentiated cancer (WDC) but not late-stage poorly differentiated cancer (PDC)., according to the University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine(1)
In advanced prostate cancer stem-like cells, sulforaphane showed to inhibit tumor engraftment and tumor growth, without the induction of liver necrosis or other obvious side effects, In vivo(2).
In the comparison of the effect of sulforaphane(SFN) and 3,3'-diindolylmethane(DIM) in normal prostate epithelial cells and prostate cancer cells, researchers at the Oregon State University found that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression(3).
References
(1) Chemoprevention of prostate cancer by d,l-sulforaphane is augmented by pharmacological inhibition of autophagy by Vyas AR1, Hahm ER, Arlotti JA, Watkins S, Stolz DB, Desai D, Amin S, Singh SV.(PubMed)
(2) Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells by Labsch S, Liu L, Bauer N, Zhang Y, Aleksandrowicz E, Gladkich J, Schönsiegel F, Herr I.(PubMed)
(3) Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells by Wong CP1, Hsu A1, Buchanan A2, Palomera-Sanchez Z1, Beaver LM1, Houseman EA2, Williams DE3, Dashwood RH3, Ho E4.(PubMed)
11. Sulforaphane and colon cancer
Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way. Bowel cancer is the third most commonly diagnosed cancer in developed countries, including US and Canada.
According to 1INRA, Laboratoire des Xénobiotiques, sulforaphane inhibited colon cancer cell line (HT29) through cell cycle arrest via an apoptotic process(1). GE132+Natural, a novel supplement consisting Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly, in the testing of tested cancer cell lines (PC3, MCF7 and SW480), is found to be effective in inhibiting all tested cancer cell proliferation, the University of Belgrade insisted(2). Other study also showed the effective of sulforaphane and related dietary isothiocyanates in treating colon cancer cells via included cell growth arrest, autophagy and apoptosis depending to Depending on the isothiocyanates (ITCs) and treatment conditions(3).
References
(1) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells by Gamet-Payrastre L1, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gasc N, Tulliez J, Tercé F.(PubMed)
(2) GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells by Okic-Djordjevic I1, Trivanovic D, Krstic J, Jaukovic A, Mojsilovic S, Santibanez JF, Terzic M, Vesovic D, Bugarski D.(PubMed)
(3) HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates by Rajendran P1, Kidane AI, Yu TW, Dashwood WM, Bisson WH, Löhr CV, Ho E, Williams DE, Dashwood RH.(PubMed)
12. Sulforaphane and cervical cancer
Cervix is the lower part of uterus that opens at the top of the vagina. Cervix acts an transition area for vaginal lining (squamous epithelium) change to uterus type (columnar epithelium) through the transitional area (squamous columnar epithelium) to host the development of the fetus. Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA.
According to the Manipal University in the study of the effect of sulforaphane and eugenol effects on human cervical cancer cells, found that combined treatment with variable dose combinations resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction(1). The Manipal University also showed that application of SFN inhibited human cervical cancer cell lines through apoptosis induction and anti-inflammatory properties(2). In human cervical carcinoma HeLa, treatment with SFN inhibit the cancer cell through down-regulation of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax expression(3).
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References
(1) Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells by Hussain A1, Priyani A, Sadrieh L, Brahmbhatt K, Ahmed M, Sharma C.(PubMed)
(2) Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells by Sharma C1, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A.(PubNed)
(3) Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3 by Park SY1, Kim GY, Bae SJ, Yoo YH, Choi YH.(PubMed)
The study of the hepatoprotective drug anisyldithiolthione was showed to be effective in acting as hepoprotective agent in inhibited lipid peroxidation induced in rat liver microsomes either chemically by FeSO4 and reducing agents (cysteine or ascorbate) or enzymatically, probably through the presence of its dithiolthione function(1) Other medication such as Anethol dithiolthione (ADT), usually prescribed as a choleretic drug, also exhibited an hepatoprotective potency at doses as low as 10 mg/kg relative to serum aminotransferase activities and hepatic glutathione related enzyme system in in Swiss female mice(2)
References
(1) A new potent inhibitor of lipid peroxidation in vitro and in vivo, the hepatoprotective drug anisyldithiolthione by Mansuy D, Sassi A, Dansette PM, Plat M.(PubMed)
(2) Protective effect of anethol dithiolthione against acetaminophen hepatotoxicity in mice by Warnet JM1, Christen MO, Thevenin M, Biard D, Jacqueson A, Claude JR.(PubMed).
2. Isothiocyanates and cancers
Cancer is a class of diseases in which a group of cells growing and multiplying disordered and uncontrollable way in our body, have become progressively worse and damaged other healthy tissues, sometimes spreads to other organs in the body via lymph or blood and results may be in death.
In a case-control study conducted in urban Shanghai. The cases (from December 2006 to December 2008, ITC consumption from cruciferous vegetables intake showed a positive effect in reduce risk of pancreatic cancer after adjusting for possible confounding factors such as age, sex, history of diabetes and pancreatitis(1). Thiazolo, the synthesis of a novel class of quinazoline, produced by the reaction of 4,6-dichloro-5-aminopyrimidine with isothiocyanates in presence of 20 mol% KF/alumina, showed to exhibit antiproliferative activity in lung (NCI-H322 and A549), epidermal (A431) and glioblastoma (T98G), HL-60 cell lines at 20 μM. The effect of compound 4a on mitochondrial potential loss in HL-60 cells probably through cleavage of PARP-1 and procaspase-3 inhibition(2).
The study by Campus Morro do Cruzeiro suggested that the phytochemical inhibited the cell viability of human cervical cancer cells, human pancreatic cancer cells, human hepatocellular carcinoma cells, human ovarian cancer cells, and have antiinflammatory properties in the treatment of human T-cell leukemia cells(3).
References
(1) [A case-control study on the association between urinary levels of isothiocyanates and the risk of pancreatic cancer].[Article in Chinese] by Wang J1, Han L, Zhang W, Wang J, Ni Q, Shen M, Gao Y2.(PubMed)
(2) Synthesis, antiproliferative and apoptosis-inducing activity of thiazolo[5,4-d]pyrimidines by Singh B1, Guru SK, Kour S, Jain SK, Sharma R, Sharma PR, Singh SK, Bhushan S, Bharate SB, Vishwakarma RA.(PubMed)
(3) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
3. Isothiocyanates as Antioxidants
Free radicals are atoms, molecules, or ions with unpaired electrons through chemical bonds with other atoms or molecules during a chemical reaction. They may have positive, negative or zero charge. The unpaired electrons cause radicals to be highly chemically reactive in the human body, leading to aging and cancers.
In Fuchs endothelial corneal dystrophy (FECD), an oxidative stress disorder, treatment with Sulforaphane, a molecule within the isothiocyanate group, decreased CEC apoptosis by 55% in unstressed group and by 43% in tBHP-treated specimens, through inhibition of oxidative stress(1).
The Universidade Federal de Ouro Preto study also indicated the similar result of sulforaphane in improvement of antioxidant status in the testing of number of cancer cell lines(2). Other study suggested that isothiocyanates (ITCs), found abundantly in cruciferous vegetables, may be effective as a cancer chemopreventive agent through modulation of phase II detoxifying/antioxidant enzyme activities(3).
Reference
(1) Sulforaphane decreases endothelial cell apoptosis in fuchs endothelial corneal dystrophy: a novel treatment by Ziaei A1, Schmedt T, Chen Y, Jurkunas UV.(PubMed)
(2) The anti-oxidant properties of isothiocyanates: a review by de Figueiredo SM1, Filho SA, Nogueira-Machado JA, Caligiorne RB.(PubMed)
(3) Structural influence of isothiocyanates on the antioxidant response element (ARE)-mediated heme oxygenase-1 (HO-1) expression by Prawan A1, Keum YS, Khor TO, Yu S, Nair S, Li W, Hu L, Kong AN.(PubMed)
4. Isothiocyanates and heart diseases
Beside cancer, heart disease kills more than 2,000 Americans everyday. Approximately 60 million Americans have heart disease.
There are many causes of heart diseases. Most of heart diseases are caused by high blood pressure contributes to hardening of the arteries. High levels of bad cholesterol (LDL) build up in the arteries as a result of uncontrolled diet with high levels of saturated fat and trans fat.
In human immunodeficiency virus (HIV) patients, showed to improve AIDS-related heart dysfunction through inhibition of apoptosis by decreasing iNOS and Bax expression through suppression of NF-κB.(1). In ischemic injury of hearts patients, showed to inhibit reactive oxygen species mediators in exerting a toxic effect during ischemia-reperfusion through mitochondrial K(ATP) channels and antioxidant pathway(2). On ischaemia-reperfusion-induced cardiac injury. steamed broccoli showed a superior cardioprotective properties over cooked broccoli, probably through through the redox signalling of sulphoraphane(3). the phytochemical also found to trduce risk of vascular disease due to aging by inhibiting oxidative stress (4).
References
(1) Isothiocyanates ameliorate the symptom of heart dysfunction and mortality in a murine AIDS model by inhibiting apoptosis in the left ventricle. by Ho JN1, Yoon HG, Park CS, Kim S, Jun W, Choue R, Lee J.(PubMed)
(2) Sulforaphane protects ischemic injury of hearts through antioxidant pathway and mitochondrial K(ATP) channels.by Piao CS1, Gao S, Lee GH, Kim do S, Park BH, Chae SW, Chae HJ, Kim SH.(PubMed)
(3) Comparison of the protective effects of steamed and cooked broccolis on ischaemia-reperfusion-induced cardiac injury. by Mukherjee S1, Lekli I, Ray D, Gangopadhyay H, Raychaudhuri U, Das DK.(PubMed)
(4) Crosstalk between Nrf2 and the proteasome: therapeutic potential of Nrf2 inducers in vascular disease and aging by Chapple SJ1, Siow RC, Mann GE.(PubMed)
5. Isothiocyanates and neuroprotective effect
Sulforaphane, a naturally organosulfur compound found in broccoli, showed to exert its neuroprotective effects through significantly attenuated the scopolamine-induced memory impairment and improved cholinergic system reactivity, as indicated by an increased ACh level, decreased AChE activity, and increased choline acetyltransferase (ChAT) expression in the hippocampus and frontal cortex(1). in a variety of acute and chronic neurodegenerative diseases, phytochemicals, isothiocyanate sulforaphane, derived from the hydrolysis of the glucosinolate glucoraphanin mainly present in Brassica vegetables, demonstrated its neuroprotective effects in several in vitro and in vivo studies, may be mainly ascribed to its peculiar ability to activate the Nrf2/ARE pathway(2). In dopaminergic neurotoxicity in mice induced by 6-hydroxydopamine (6-OHDA), the phytochemical showed the neuroprotective effect through its ability to enhance glutathione levels and its dependent enzymes (glutathione-S-transferase and glutathione reductase) and to modulate neuronal survival pathways(3).
References
(1) Sulforaphane alleviates scopolamine-induced memory impairment in mice by Lee S1, Kim J1, Seo SG2, Choi BR3, Han JS3, Lee KW4, Kim J5.(PubMed)
(2) Sulforaphane as a potential protective phytochemical against neurodegenerative diseases byTarozzi A1, Angeloni C, Malaguti M, Morroni F, Hrelia S, Hrelia P.(PubMed)
(3) Neuroprotective effect of sulforaphane in 6-hydroxydopamine-lesioned mouse model of Parkinson's disease byMorroni F1, Tarozzi A, Sita G, Bolondi C, Zolezzi Moraga JM, Cantelli-Forti G, Hrelia P.(PubMed)
6. Sulforaphane and Obesity
Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.
Taking foods containing sulforaphane may be effective in managing weight loss for obese patients accompanied with change of lifestyle with more vegetables and fruits into diet. Sulforaphane, a molecule within the isothiocyanate group, according to Chungbuk National University, showed to prevent high-fat diet (HFD)-induced obesity in C57BL/6N mice. through inhibiting adipogenesis( the cells differentiation for a vital role in energy homeostasis and process the largest energy reserve in the body of animals). via down-regulation of PPARγ(regulation of metabolism) and C/EBPα (inflammatory process) and by suppressing lipogenesis( protein as an intermediate stage in metabolism of simple sugars) through activation of the AMPK(in cellular energy homeostasis) pathway(1). Chronic oral administration of sulforaphane, on obesity and insulin resistance induced by a highly palatable (HP) diet in male Wistar rats, at the specific dose was able to accentuate glucose intolerance and may affect GLUT3 expression involed neuronal glucose transport in the cerebral cortex and hypothalamus(2). The Chonbuk National University also suggested that Sulforaphane suppressed AMPK phosphorylation(cellular energy homeostasis) at Thr-172 in a dose-dependent manner(3).
References
(1) Sulforaphane attenuates obesity by inhibiting adipogenesis and activating the AMPK pathway in obese mice by Choi KM1, Lee YS1, Kim W1, Kim SJ2, Shin KO1, Yu JY3, Lee MK1, Lee YM1, Hong JT1, Yun YP1, Yoo HS4.(PubMed)(2) Chronic sulforaphane oral treatment accentuates blood glucose impairment and may affect GLUT3 expression in the cerebral cortex and hypothalamus of rats fed with a highly palatable diet by Souza CG1, Riboldi BP, Hansen F, Moreira JD, Souza DG, de Assis AM, Brum LM, Perry ML, Souza DO.(PubMed)
(3) Sulforaphane induced adipolysis via hormone sensitive lipase activation, regulated by AMPK signaling pathway by Lee JH1, Moon MH, Jeong JK, Park YG, Lee YJ, Seol JW, Park SY.(PubMed)
7. Sulforaphane and Lung diseases
Lung diseases is defined as a condition, affecting the upper respiratory tract, trachea, bronchi, bronchioles, alveoli, pleura and pleural cavity, and the nerves and muscles of breathing.
Sulforaphane may be used as a preventive chemical constituent of pulmonary damage for patient who exposure to arsenic. According to China Medical University, arsenic-containing dust resulted in ; all of which were blocked by sulforaphane (SF) blocked pathological alterations, oxidative DNA damage, and mild apoptotic cell death in the lung caused by 2 weeks of exposure to arsenic through activation of Nrf2(master regulator of the total antioxidant system)(1). In wildtype neonatal mice exposed to hyperoxia. SF also found to activated Nrf2 activation through induced expression of anti-oxidant genes,(2). In the lungs of the arrhythmic Clock(Δ19) mice, SF also activated it anti ovidative damage effect through activation of NRF2/glutathione defense pathway in combating oxidative/fibrotic lung damage(3).
References
(1) Sulforaphane prevents pulmonary damage in response to inhaled arsenic by activating the Nrf2-defense response. by Zheng Y1, Tao S, Lian F, Chau BT, Chen J, Sun G, Fang D, Lantz RC, Zhang DD.(PubMed)
(2) Transcriptional responses of neonatal mouse lung to hyperoxia by Nrf2 status by McGrath-Morrow SA1, Lauer T, Collaco JM, Lopez A, Malhotra D, Alekseyev YO, Neptune E, Wise R, Biswal S.(PubMed)
(3) The circadian clock regulates rhythmic activation of the NRF2/glutathione-mediated antioxidant defense pathway to modulate pulmonary fibrosis by Pekovic-Vaughan V1, Gibbs J, Yoshitane H, Yang N, Pathiranage D, Guo B, Sagami A, Taguchi K, Bechtold D, Loudon A, Yamamoto M, Chan J, van der Horst GT, Fukada Y, Meng QJ.(PubMed)
8. Sulforaphane and Liver disease
Liver disease in most cases are linked to alcohol or drugs. In fact, it can be caused by a variety of factors and affecting everyone from infants to older adults.
In CYP2E1-dependent binge alcohol-induced liver steatosis, oral treatment of sulforphane sulforaphane showed to activated Nrf2, increased levels of the Nrf2 target heme oxygenase-1 and subsequently lowered oxidant stress as shown by the decline in lipid peroxidation and 3-nitrotyrosine protein adducts and an increase in GSH levels(1). In the comparison of the effectiveness of Sulforaphane and glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells, Dr Abdull Razis AF1, and Noor NM found that sulforphane is superior to glucoraphanin in modulators of various phase I and phase II enzymes involved in carcinogen-metabolising enzyme systems in vitro(2). The University of Rhode Island, Kingston study also insisted that SF activate Nrf2 activation in inhibited lipid accumulation in white adipose tissue, suppressed adipogenesis, induced insulin resistance and glucose intolerance, and increased hepatic steatosis in Lep(ob/ob) mice(3)..
References
(1) Sulforaphane induces Nrf2 and protects against CYP2E1-dependent binge alcohol-induced liver steatosis by Zhou R1, Lin J, Wu D.(PubMed)
(2) Sulforaphane is superior to glucoraphanin in modulating carcinogen-metabolising enzymes in Hep G2 cells by Abdull Razis AF1, Noor NM.(PubMed)
(3) Enhanced Nrf2 activity worsens insulin resistance, impairs lipid accumulation in adipose tissue, and increases hepatic steatosis in leptin-deficient mice by Xu J1, Kulkarni SR, Donepudi AC, More VR, Slitt AL.(PubMed)
9. Sulforaphane and Breast cancer
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The University of Michigan, also insisted that ingestion of sulforaphane at a dose of 50 mg/kg for 2 weeks inhibited breast cancer stem cells(1). According to Manipal University, Sulforaphane inhibited growth of human breast cancer cell line MCF-7 cells, through induces apoptosis and anti-inflammatory effects on MCF-7 cells via downregulation of Bcl-2 (anti-apoptotic protein) and COX-2 (inlvoved inflammatory process) respectively(2). Also in testing of MCF-7 breast cancer cells, researchers at the The Catholic University of Korea, showed that sulforaphane induced the inhibition of 12-O-tetradecanoyl phorbol-13-acetate (TPA)-induced MMP-9 expression(involved in keratinocyte migration and granulation tissue remodeling during wound healing) and cell invasion by via the suppression of the NF-κB (nvolved in cellular responses)pathway in MCF-7 cells(3).
References
(1) Sulforaphane, a dietary component of broccoli/broccoli sprouts, inhibits breast cancer stem cells by Li Y1, Zhang T, Korkaya H, Liu S, Lee HF, Newman B, Yu Y, Clouthier SG, Schwartz SJ, Wicha MS, Sun D.(PubMed)
(2) Sulforaphane inhibits growth of human breast cancer cells and augments the therapeutic index of the chemotherapeutic drug, gemcitabine by Hussain A1, Mohsin J, Prabhu SA, Begum S, Nusri Qel-A, Harish G, Javed E, Khan MA, Sharma C.(PubMed)
(3) Sulforaphane controls TPA-induced MMP-9 expression through the NF-κB signaling pathway, but not AP-1, in MCF-7 breast cancer cells by Lee YR1, Noh EM, Han JH, Kim JM, Hwang BM, Kim BS, Lee SH, Jung SH, Youn HJ, Chung EY, Kim JS.(PubMed)
10. Sulforaphane and Prostate cancer
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth which spread to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during the Physical (rectum) exams.
Oral administration of d,l-sulforaphane (SFN) can decrease the incidence or burden of early-stage prostate cancer [prostatic intraepithelial neoplasia (PIN)] and well-differentiated cancer (WDC) but not late-stage poorly differentiated cancer (PDC)., according to the University of Pittsburgh Cancer Institute and University of Pittsburgh School of Medicine(1)
In advanced prostate cancer stem-like cells, sulforaphane showed to inhibit tumor engraftment and tumor growth, without the induction of liver necrosis or other obvious side effects, In vivo(2).
In the comparison of the effect of sulforaphane(SFN) and 3,3'-diindolylmethane(DIM) in normal prostate epithelial cells and prostate cancer cells, researchers at the Oregon State University found that SFN and DIM reversed many of the cancer-associated methylation alterations, including aberrantly methylated genes that are dysregulated or are highly involved in cancer progression(3).
References
(1) Chemoprevention of prostate cancer by d,l-sulforaphane is augmented by pharmacological inhibition of autophagy by Vyas AR1, Hahm ER, Arlotti JA, Watkins S, Stolz DB, Desai D, Amin S, Singh SV.(PubMed)
(2) Sulforaphane and TRAIL induce a synergistic elimination of advanced prostate cancer stem-like cells by Labsch S, Liu L, Bauer N, Zhang Y, Aleksandrowicz E, Gladkich J, Schönsiegel F, Herr I.(PubMed)
(3) Effects of sulforaphane and 3,3'-diindolylmethane on genome-wide promoter methylation in normal prostate epithelial cells and prostate cancer cells by Wong CP1, Hsu A1, Buchanan A2, Palomera-Sanchez Z1, Beaver LM1, Houseman EA2, Williams DE3, Dashwood RH3, Ho E4.(PubMed)
11. Sulforaphane and colon cancer
Bowel cancer is relatively very common and slowly growing and progress cancer and in predictable way. Bowel cancer is the third most commonly diagnosed cancer in developed countries, including US and Canada.
According to 1INRA, Laboratoire des Xénobiotiques, sulforaphane inhibited colon cancer cell line (HT29) through cell cycle arrest via an apoptotic process(1). GE132+Natural, a novel supplement consisting Resveratrol, Ganoderma lucidum, Sulforaphane, Lycopene and Royal jelly, in the testing of tested cancer cell lines (PC3, MCF7 and SW480), is found to be effective in inhibiting all tested cancer cell proliferation, the University of Belgrade insisted(2). Other study also showed the effective of sulforaphane and related dietary isothiocyanates in treating colon cancer cells via included cell growth arrest, autophagy and apoptosis depending to Depending on the isothiocyanates (ITCs) and treatment conditions(3).
References
(1) Sulforaphane, a naturally occurring isothiocyanate, induces cell cycle arrest and apoptosis in HT29 human colon cancer cells by Gamet-Payrastre L1, Li P, Lumeau S, Cassar G, Dupont MA, Chevolleau S, Gasc N, Tulliez J, Tercé F.(PubMed)
(2) GE132+Natural: Novel promising dietetic supplement with antiproliferative influence on prostate, colon, and breast cancer cells by Okic-Djordjevic I1, Trivanovic D, Krstic J, Jaukovic A, Mojsilovic S, Santibanez JF, Terzic M, Vesovic D, Bugarski D.(PubMed)
(3) HDAC turnover, CtIP acetylation and dysregulated DNA damage signaling in colon cancer cells treated with sulforaphane and related dietary isothiocyanates by Rajendran P1, Kidane AI, Yu TW, Dashwood WM, Bisson WH, Löhr CV, Ho E, Williams DE, Dashwood RH.(PubMed)
12. Sulforaphane and cervical cancer
Cervix is the lower part of uterus that opens at the top of the vagina. Cervix acts an transition area for vaginal lining (squamous epithelium) change to uterus type (columnar epithelium) through the transitional area (squamous columnar epithelium) to host the development of the fetus. Cervical cancer is malignant neoplasm of the cervix uteri or cervical area caused by abnormal cells growth with alternation of cells DNA.
According to the Manipal University in the study of the effect of sulforaphane and eugenol effects on human cervical cancer cells, found that combined treatment with variable dose combinations resulted in differential effects with an antagonistic effect at lower and synergistic at higher sub-lethal doses as reflected in cell cytotoxicity and apoptosis induction(1). The Manipal University also showed that application of SFN inhibited human cervical cancer cell lines through apoptosis induction and anti-inflammatory properties(2). In human cervical carcinoma HeLa, treatment with SFN inhibit the cancer cell through down-regulation of anti-apoptotic Bcl-2 and Bcl-XL, and the up-regulation of pro-apoptotic Bax expression(3).
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Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) Concurrent sulforaphane and eugenol induces differential effects on human cervical cancer cells by Hussain A1, Priyani A, Sadrieh L, Brahmbhatt K, Ahmed M, Sharma C.(PubMed)
(2) Anti-carcinogenic effects of sulforaphane in association with its apoptosis-inducing and anti-inflammatory properties in human cervical cancer cells by Sharma C1, Sadrieh L, Priyani A, Ahmed M, Hassan AH, Hussain A.(PubNed)
(3) Induction of apoptosis by isothiocyanate sulforaphane in human cervical carcinoma HeLa and hepatocarcinoma HepG2 cells through activation of caspase-3 by Park SY1, Kim GY, Bae SJ, Yoo YH, Choi YH.(PubMed)
Friday, May 23, 2014
Adionection and Obesity complications
Recent sudy from the renowned institutions suggested that protein Adiponectin may be associated to risk of obesity. Adionection is a protein with function involved in regulating glucose levels as well as fatty acid breakdown. Therefore, it plays a causal role in the development of insulin resistance and cardiovascular disease.
Obesity is defined as a medical condition of excess body fat has accumulated overtime, while overweight is a condition of excess body weight relatively to the height. According to the Body Mass Index(BMI), a BMI between 25 to 29.9 is considered over weight, while a BMI of over 30 is an indication of obesity. According to the statistic, 68% of American population are either overweight or obese.
In a study of all the fourth-grade school children (9 or 10 years of age) in the town of Ina during 2005-2008 (N = 1675), Japan, lower levels of adiponectin complexes were associated to in the abdominal obesity group than in the non-abdominal obesity group regardless of sex. In fact the impact of abdominal obesity was larger in boys than in girls(1).
Indeed, the alternation and mutation of adiponectin gene were also found to contribute to the genetic risk towards the development of in the south Indian population study by the Madras Diabetes Research Foundation-ICMR Advanced Centre for Genomics of Type 2 Diabetes and Dr. Mohan's Diabetes Specialities Centre(2).
But in the study of calorie-restricted low-fat and low-carbohydrate diets (LFD and LCD among overweight and obese premenopausal women, researchers suggested that in these diet patterns serum leptin, but not adiponectin is found to effect on obesity's complications(3). In support of the above, the West China Medical School study showed that Leptin, the product of the obese gene, is an adipocyte-secreted protein hormone playing a key role in the progression of obesity(4)
The Russian study indicated the evaluation of metabolic disorders and adipokine synthesis in obese patients may optimize the diagnosis of type 2 diabetes mellitus and cardiovascular diseases and to personalize diet therapy(5).
Taken altogether, adipokine synthesis is associated to risk of obesity, but the question of low level of adiponectin levels induced obesity or obesity induced lower levels of adiponectin is remained unknown. Leptin, another member of adipokine may be used biomarker in manage the progression of the disease and its complications. As always, all articles written by Kyle J. Norton are for information & education only, please consult your Doctor & Related field specialist before applying
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Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) Abdominal obesity and serum adiponectin complexes among population-based elementary school children in Japan: a cross-sectional study by Ochiai H1, Shirasawa T, Nishimura R, Nanri H, Ohtsu T, Hoshino H, Tajima N, Kokaze A.(PubMed)
(2) Genetic association of ADIPOQ gene variants with type 2 diabetes, obesity and serum adiponectin levels in south Indian population by Ramya K1, Ayyappa KA, Ghosh S, Mohan V, Radha V.(PubMed)
(3) Favorable effects of low-fat and low-carbohydrate dietary patterns on serum leptin, but not adiponectin, among overweight and obese premenopausal women: a randomized trial by Llanos AA1, Krok JL2, Peng J3, Pennell ML3, Olivo-Marston S1, Vitolins MZ3, Degraffinreid CR2, Paskett ED(PubMed)
(4) Synthesis and biological evaluation of novel urea- and guanidine-based derivatives for the treatment of obesity-related hepatic steatosis by Liang X1, Pei H2, Ma L3, Ran Y4, Chen J5, Wang G6, Chen L5.(PubMed)
(5) [Adipokines and the metabolism of key nutrients in patients with obesity].
[Article in Russian] by Kirillova OO, Vorozhko IV, Gapparova KM, Chekhonina IuG, Sentsova TB, Tutel'ian VA.(PubMed)
The Science of Soy - The East, West and East-West Viewpoints
Soy foods, including tofu have been in traditional Chinese diet over thousands of year, according to Chinese literature. The reduced risk of chronic disease, including metabolic syndrome such as cardiovascular diseases, obesity and diabetes and lesser menopause symptoms in advanced age, may be aided by eating a lot of soy food accompanied with large portion of vegetables and fruits. Indeed, according to the study, only 10% of women in the East are experience symptoms of menopause in advanced age compared to over 70% of their Western counterparts.
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8 to 12.8%7 of total protein intake in older adult in Japan.(b)
The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences can be seen by walking through the supermarkets and drug stores. Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers are widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.
Today, the promotion of soy are no longer existed, it may be results of discovery of adverse effect in single ingredient and animal studies, as intake of soy is associated to induce risk certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty.
Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.
Nutrients
1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.
Phytochemicals
1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein
I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(1). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(1a)(1b)
A.1. Soy and the risk of cerebral infarction (CI) and myocardial infarction (MI) in Japan population
The searching of the Keywords in PubMed, soy and heart diseases and stroke in Japan found 3 studies, all showed the positive effect of soy in reduced risk heart disease and stroke.
Cerebral infarction (CI) is defined as a type of ischemic stroke due to blockage in the blood vessels supplying blood to the brain.
Myocardial infarction (MI) is also known as heart attack. It is defined as a condition of blood stop flowing properly to part of the heart as a result of not receiving enough oxygen.
According to National Cardiovascular Center, Japan, the studied 40,462 Japanese (40 to 59 years old, without cardiovascular disease or cancer at baseline), yields interest results.
People who consume more soy are less likely to be current smokers but more likely to be hypertensive, with men are more likely to have diabetes mellitus. The frequency of soy intake was positively related to daily intake of rice, vegetables, fruits, fish, potassium, calcium, carbohydrate, polyunsaturated fatty acid, saturated fatty acid, fiber, and isoflavones for both sexes.
The study started in the 1990 with food-frequency questionnaire included 44 foods with 3 questions to assess soy, bean, and miso consumption. The 1995 follow-up questionnaire covered 147 foods with 8 questions on soy products.
The result is astonishing, during a follow-up period that averaged 12.5 years, 1230 strokes were documented, of which 1137 were confirmed through imaging or autopsy, even high isoflavone intake was associated with reduced risk of CI and MI in middle-aged Japanese subjects, but not in men and dietary isoflavones and may be beneficial to postmenopausal women for the prevention of ischemic CVD(2). Intake of miso soup although showed to reduce risk of hypertension but did not contributed to ischemic CVD mortality in either men or women.
Strong evidence of epidemiological studies from the East and West has shown that hyperlipidemia is a major risk factor in contribution to heart diseases, notably on intermediate end points(3)(4). Soy foods intake has been known to contain lowering cholesterol and blood pressure effect. According to the Veterans Affairs Medical Center, daily soy protein showed a significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.(4). But the study suggested that the mechanism of reduced risk of cerebral infarction (CI) and myocardial infarction (MI) for postmenopausal Japanese women may not be through reduction of lipid profile but through exposure to a large quantity of isoflavones, which act as estrogen agonist because estrogen receptors are not occupied with plasma estradiol in postmenopausal women.
In case of hypertension in the subject of study, although the disease have been shown to contribute to the early risk factor for the progression heat disease and stroke(6)(7)(8)(9). Consumption of soy has no effect in reduce risk of the development of cerebral infarction (CI) and myocardial infarction for people with histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia, even soy has shown effectively in reduced high blood pressure(12)
In support to the above, the dietary intervention study targeting female students by using cake containing soybean protein and isoflavone at the Mukogawa Women's University, 4 weeks dietary intake of soy protein found to reduce CHD risk among Japanese female students with a high plasma cholesterol level(10) and Dr. Nagata C. at the Gifu University School of Medicine, Gifu, Japan, in the study of association between soy product intake and mortality from cancer and heart disease in Japan, suggested that soy foods intake showed a preventive role in against stomach cancer and heart disease death(11).
Dr. Yoshihiro Kokubo and the research team also acknowledged the limitation of the study such as ethic group, measurement errors with nutrient intake or due to it self report, but insisted that nationwide annual health screenings may ease the self report concern.
They also clarified that the result of the study of dietary intake of isoflavones, are not relevant to the association of isoflavone supplement use with ischemic CVD.
In deed, the effectives of soy isoflavone in reduced risk of cerebral infarction (CI) and myocardial infarction in this case, yield some questions due to it ethnicity.
a. If soy is found to effective in reduce risk of hypertension and hyperlipidemia, why it does not contribute to the reduce risk of cerebral infarction (CI) and myocardial infarction in men with histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia.
Would the medication is the cause? As epidemiological study insisted the lowering effect of blood pressure and cholesterol are associated to reduce risk heart disease and stroke.
b. Although soy isoflavone showed an effectiveness in reduce risk of cerebral infarction (CI) and myocardial infarction and mortality, would dietary with high in fruit and vegetable also best known for the reduce risk of heart disease and stroke be also taken into account?
c. The effectiveness of the study may only be true for equol producers population as 90% of subjects' study are equol producers?
b. Would the "Japanese Phenomenon" interfere with the study, as administration of isoflavone "inexperienced" women at the time of menopause, the phytoestrogens appear to share the same effects as estrogen used in classical preparations for hormone replacement therapy?
References
(a) The Science of Soy: What Do We Really Know? by Julia R. Barrett
(b) Guideline for healthy soy intake(the Unite Soybean board)
(1) Japan, Wikipedia
(1a) Erdman JW Jr. AHA Science Advisory: soy protein and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation. 2000; 102: 2555–2559
(Soy protein and cardiovascular disease)
(1b) van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation. 2005; 111: 465–471(Cardiovascular diseases in women)
(5) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population by Nagata C1, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Inoue M, Tsugane S, Sasazuki S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan.(PubMed)
(6) Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study by Toi M1, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T, Tokuda Y, Masuda N, Ohsumi S, Ohno S, Takahashi M, Hayashi H, Yamamoto S, Ohashi Y.(PubMed)
(7) Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women by Tsuji M1, Tamai Y, Wada K, Nakamura K, Hayashi M, Takeda N, Yasuda K, Nagata C.(PubMed)
(8) Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group by Iwasaki M1, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, Yamamoto S, Tsugane S; Japan Public Health Center-based prospective study group.(PubMed)
(9) Isoflavones--safe food additives or dangerous drugs? by Wuttke W1, Jarry H, Seidlová-Wuttke D.(PubMed)
(10) Effect of a soybean product on serum lipid levels in female university students by Takahashi K1, Kamada Y, Hiraoka-Yamamoto J, Mori M, Nagata R, Hashimoto K, Aizawa T, Matsuda K, Kometani T, Ikeda K, Yamori Y.(PubMed)
(11) Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan by Nagata C.(PubMed)
(12) Association of blood pressure with intake of soy products and other food groups in Japanese men and women by Nagata C1, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K.(PubMed)
(14) Effects of dietary intake of soy protein and isoflavones on cardiovascular disease risk factors in high risk, middle-aged men in Scotland by Sagara M1, Kanda T, NJelekera M, Teramoto T, Armitage L, Birt N, Birt C, Yamori Y.(PubMed)
A.2. Soy and Breast cancer in Japanese women
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The searching of keyword in PubMed with keywords, soy and breast cancer in Japanese women, found 15 related studies.
Epidemiologic evidence suggesting high intake of soy in Japanese population is associated to reduce risk of breast cancer(1) and regular consumption of probiotic beverage and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women(2)(2a).
The study in the testing of oral administration of IF-rich tablet (20 and 40 mg/day) on climacteric women, showed the product not only reduced risk of breast cancer but also showed an improvement of bone density, hypertension and climacteric symptoms, cardiovascular diseases, gynecological problems and possible immune potentiation(3)
Japanese women show lower incidence of and mortality from breast cancer, compared to Caucasians, it may be result of large amount intake soy protein and isoflavones, as high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects(4).
According to the Loma Linda University, Asian population consumes as much as 25 g of soy protein or 100 mg of isoflavones per day(5).
Epidemiological Western studies have link levels of Genistein and daidzein in stimulating breast tumor growth and antagonize the effects of tamoxifen have been inclusive. Some researchers suggested that women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products(6).
In Japanese population, serum of isoflavones and insulin levels were not associated with breast cancer risk, in a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, of serum isoflavone, insulin and adiponectin levels with breast cancer risk(7).
The review of Soy for breast cancer survivors, also rejected the above claim of adult consumption of soy affects the risk of developing breast cancer or that soy consumption affects the survival of breast cancer patients(8). In deed, in Japanese study in testing the serum concentrations of genistein and daidzein, showed urinary excretion in 10 women and 9 men who consumed a typical low-fat diet with much rice and soy products, fish, and vegetables, in a rural village south of Kyoto, Japan, indicated a co-related to isoflavonoids intake and serum concentrations of genistein and daidzein and suggested that these may be a result of low mortality in breast and prostate cancer of Japanese women and men, respectively(9). In fact, tofu is found to be associated with the serum concentrations of genistein and daidzein but fermented product, such as miso showed a slight association with serum concentrations of these phytoestrogens with serum concentrations of equol showed associated with dietary intake of tofu and miso soup(10).
Soymilk, a flavor drink on breakfast in Asian diet, when conbined with combination with probiotic Lactobacillus casei Shirota (LcS) also showed to prevent the development of mammary tumors through suppressesion of tumor growth and might be a beneficial dietary style for breast cancer prevention(11). Intake of soy combined with seaweed in equol producers, showed seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria, in healthy postmenopausal women(12). In premenopausal Japanese women study with randomly assigned to receive either a soymilk-supplemented diet (n = 31) or a normal (control) diet (n = 29), involved three consecutive menstrual cycles showed the estrone and estradiol levels were decreased by 23% and 27%, respectively, in the soymilk-supplemented group but insisted that larger studies will be required to confirm the ability of soy products to reduce serum estrogen levels(12a). Other study in 50 healthy premenopausal Japanese women, also showed a similar result as blood samples drawn from each subject on Days 11 and 22 of her menstrual cycle, suggested that the consumption of soy products lowers the risk of developing breast cancer risk in modifying estrogen metabolism(12b).
In postmenopausal Japanese women, according to the study from the Takayama, with participants members aged 35 years or older in 1992 with follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008, concluded that soy and isoflavone intakes may have a protective effect on postmenopausal breast cancer. Risks of breast cancer were decreased among women with a moderate intake of soy and isoflavone(13).
In a total of 678 breast cancer cases and 3,390 age- and menopausal status-matched noncancer controls, soy showed a protective effect against breast cancer risk differs by receptor status, including with ER-positive (ER+) and HER2-negative (HER2-)(14). Genistein a major component of soybean isoflavone, has been found to induce breast cancer in some Western study, also exert its anti breast cancer preventive effect in a breast cancer cell overexpressing HER-2, as genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt which plays a key role in multiple cellular processes in combined with chemotherapeutic agent (15).
Unfortunately, report on a Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features, suggested that consumption of soy food has no protective effects against breast cancer, but insisted that further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer(16).
According to DR. Nagata C. the protective risk against breast cancer only found in in Asian but not Western populations with intake of soy may be due to consume levels of soy typical in Asian diets. researchers should also take account of amount of soy isoflavones consumed, the form and food source of isoflavones, timing of isoflavone exposure, estrogen receptor status of tumors, and equol-producer status and hormonal profile of individuals. These factors might explain the heterogeneity of results from studies(17).
References
(1) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population(PubMed)
(2) Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study by Toi M1, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T, Tokuda Y, Masuda N, Ohsumi S, Ohno S, Takahashi M, Hayashi H, Yamamoto S, Ohashi Y.(PubMed)
(2a) Yamamoto S1, Sobue T, Kobayashi M, Sasaki S, Tsugane S; Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases Group.(PubMed)
(3) Isoflavones for prevention of cancer, cardiovascular diseases, gynecological problems and possible immune potentiation by Watanabe S1, Uesugi S, Kikuchi Y.(PubMed)
(4) Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)
(5) Estimated Asian adult soy protein and isoflavone intakes, by Messina M1, Nagata C, Wu AH.(PubMed).
(6) Effects of soy phytoestrogens genistein and daidzein on breast cancer growth by de Lemos ML.(PubMed)
(7) Minatoya M1, Kutomi G, Asakura S, Otokozawa S, Sugiyama Y, Ohnishi H, Akasaka H, Miura T, Mori M, Hirata K.(PubMed)
(8) Soy for breast cancer survivors: a critical review of the literature by Messina MJ1, Loprinzi CL.(PubMed)
(9) Association of serum phytoestrogen concentration and dietary habits in a sample set of the JACC Study by Ozasa K1, Nakao M, Watanabe Y, Hayashi K, Miki T, Mikami K, Mori M, Sakauchi F, Washio M, Ito Y, Suzuki K, Kubo T, Wakai K, Tamakoshi A; JACC Study Group.(PubMed)
(10) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet by Adlercreutz H1, Honjo H, Higashi A, Fotsis T, Hämäläinen E, Hasegawa T, Okada H.(PubMed)
(11) Lactobacillus casei Shirota enhances the preventive efficacy of soymilk in chemically induced breast cancer by Kaga C1, Takagi A, Kano M, Kado S, Kato I, Sakai M, Miyazaki K, Nanno M, Ishikawa F, Ohashi Y, Toi M.(PubMed)
(12) Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women by Teas J1, Hurley TG, Hebert JR, Franke AA, Sepkovic DW, Kurzer MS.(PubMed)
(12a) Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women by Nagata C1, Takatsuka N, Inaba S, Kawakami N, Shimizu H.(PubMed)
(12b) Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women by Nagata C1, Kabuto M, Kurisu Y, Shimizu H.(PubMed)
(13) Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study by Wada K1, Nakamura K, Tamai Y, Tsuji M, Kawachi T, Hori A, Takeyama N, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C.(PubMed)
(14) Effect of soybean on breast cancer according to receptor status: a case-control study in Japan by Suzuki T1, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T, Yamashita T, Iwata H, Tanaka H, Tajima K.(PubMed)
(15) Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent by Satoh H1, Nishikawa K, Suzuki K, Asano R, Virgona N, Ichikawa T, Hagiwara K, Yano T.(PubMed)
(16) Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study by Nishio K1, Niwa Y, Toyoshima H, Tamakoshi K, Kondo T, Yatsuya H, Yamamoto A, Suzuki S, Tokudome S, Lin Y, Wakai K, Hamajima N, Tamakoshi A(PubMed)
(17) Factors to consider in the association between soy isoflavone intake and breast cancer risk.
(12) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet by Adlercreutz H1, Honjo H, Higashi A, Fotsis T, Hämäläinen E, Hasegawa T, Okada H.(PubMed)
(13) Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the "second human genome" by Akaza H.(PubMed)
According to Dr. Mark Messina, Ph.D., Soy foods contributed from 6.5%8 to 12.8%7 of total protein intake in older adult in Japan.(b)
The approval of cardiovascular benefit of soy by FDA in 1999 accompanied with the discovery of health benefits in clinical studies over past decade, prompted the promotion and advertisement of soy's health benefits in every aspect in Western society. Evidences can be seen by walking through the supermarkets and drug stores. Soy supplements and products such as tofu, soy milk, soy-based infant formula, and meatless “texturized vegetable protein” burgers are widely available. According to the United Soybean Board’s 2004–2005, 25% of Americans consume soy foods or beverages at least once per week, and 74% view soy products as healthy.
Today, the promotion of soy are no longer existed, it may be results of discovery of adverse effect in single ingredient and animal studies, as intake of soy is associated to induce risk certain mammary cancers and infertility. The publication of the result have drawn many criticisms. According to Thomas Badger, director and senior investigator at the Arkansas Children’s Nutrition Center in Little Rock, these effects are seen only under certain experimental conditions that are not likely to occur in humans—and therein lies the crux of the debate(a). Equol (4',7-isoflavandiol), an isoflavandiol metabolized from daidzein may be the causes, as 90% of Eastern population are equol producers but only 30% in the West.
The explanation of the positive effect of soy isoflavones in reduced risk of mammary cancers by University of Goettingen may be interesting, as researchers said" Most importantly, there is dispute as to whether isoflavones derived from soy or red clover have negative, positive or any effect at all on the mammary gland or endometrium. It is beyond any doubt that soy products may have cancer preventing properties in a variety of organs including the mammary gland. However, these properties may only be exerted if the developing organ was under the influence of isoflavones during childhood and puberty.
Soybean is genus Glycine, the family Fabaceae, one of the legumes that contains twice as much protein per acre as any other major vegetable or grain crop, native to Southeast Asia. Now, it is grown worldwide with suitable climate for commercial profits.
Nutrients
1. Carbohydrates
2. Dietary fiber
3. Fat
4. Protein
5. Essential amino acid
6. Vitamin A
7. Vitamin B6
8. Vitamin B12
9. Vitamin C
10. Vitamin K
11. Calcium
12. Iron
13. Magnesium
14. Phosphorus
15. Potassium
16. Sodium
17. Zinc
18. Etc.
Phytochemicals
1. Isoflavones
2. Genistein
3. Saponins
4. Beta-sitosterol
5. Daidzein
I. Soy in Eastern population
A. The Japanese population
Japan, an island nation in the Pacific Ocean, lies to the east of the Sea of Japan, China, North Korea, South Korea and Russia, stretching from the Sea of Okhotsk in the north to the East China Sea and Taiwan in the south(1). According to Moriyama, Japanese women and men live longer and healthier than everyone else on Earth, it may be result of healthier Japanese diet and lifestyle. According to the World Health Organization, the Japanese have an average of 75 years healthy living with disability-free, it may be due to average soy intake 10 to 70 times higher than in Western people(1a)(1b)
A.1. Soy and the risk of cerebral infarction (CI) and myocardial infarction (MI) in Japan population
The searching of the Keywords in PubMed, soy and heart diseases and stroke in Japan found 3 studies, all showed the positive effect of soy in reduced risk heart disease and stroke.
Cerebral infarction (CI) is defined as a type of ischemic stroke due to blockage in the blood vessels supplying blood to the brain.
Myocardial infarction (MI) is also known as heart attack. It is defined as a condition of blood stop flowing properly to part of the heart as a result of not receiving enough oxygen.
According to National Cardiovascular Center, Japan, the studied 40,462 Japanese (40 to 59 years old, without cardiovascular disease or cancer at baseline), yields interest results.
People who consume more soy are less likely to be current smokers but more likely to be hypertensive, with men are more likely to have diabetes mellitus. The frequency of soy intake was positively related to daily intake of rice, vegetables, fruits, fish, potassium, calcium, carbohydrate, polyunsaturated fatty acid, saturated fatty acid, fiber, and isoflavones for both sexes.
The study started in the 1990 with food-frequency questionnaire included 44 foods with 3 questions to assess soy, bean, and miso consumption. The 1995 follow-up questionnaire covered 147 foods with 8 questions on soy products.
The result is astonishing, during a follow-up period that averaged 12.5 years, 1230 strokes were documented, of which 1137 were confirmed through imaging or autopsy, even high isoflavone intake was associated with reduced risk of CI and MI in middle-aged Japanese subjects, but not in men and dietary isoflavones and may be beneficial to postmenopausal women for the prevention of ischemic CVD(2). Intake of miso soup although showed to reduce risk of hypertension but did not contributed to ischemic CVD mortality in either men or women.
Strong evidence of epidemiological studies from the East and West has shown that hyperlipidemia is a major risk factor in contribution to heart diseases, notably on intermediate end points(3)(4). Soy foods intake has been known to contain lowering cholesterol and blood pressure effect. According to the Veterans Affairs Medical Center, daily soy protein showed a significantly decreased serum concentrations of total cholesterol, LDL cholesterol, and triglycerides without significantly affecting serum HDL cholesterol concentrations.(4). But the study suggested that the mechanism of reduced risk of cerebral infarction (CI) and myocardial infarction (MI) for postmenopausal Japanese women may not be through reduction of lipid profile but through exposure to a large quantity of isoflavones, which act as estrogen agonist because estrogen receptors are not occupied with plasma estradiol in postmenopausal women.
In case of hypertension in the subject of study, although the disease have been shown to contribute to the early risk factor for the progression heat disease and stroke(6)(7)(8)(9). Consumption of soy has no effect in reduce risk of the development of cerebral infarction (CI) and myocardial infarction for people with histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia, even soy has shown effectively in reduced high blood pressure(12)
In support to the above, the dietary intervention study targeting female students by using cake containing soybean protein and isoflavone at the Mukogawa Women's University, 4 weeks dietary intake of soy protein found to reduce CHD risk among Japanese female students with a high plasma cholesterol level(10) and Dr. Nagata C. at the Gifu University School of Medicine, Gifu, Japan, in the study of association between soy product intake and mortality from cancer and heart disease in Japan, suggested that soy foods intake showed a preventive role in against stomach cancer and heart disease death(11).
Dr. Yoshihiro Kokubo and the research team also acknowledged the limitation of the study such as ethic group, measurement errors with nutrient intake or due to it self report, but insisted that nationwide annual health screenings may ease the self report concern.
They also clarified that the result of the study of dietary intake of isoflavones, are not relevant to the association of isoflavone supplement use with ischemic CVD.
In deed, the effectives of soy isoflavone in reduced risk of cerebral infarction (CI) and myocardial infarction in this case, yield some questions due to it ethnicity.
a. If soy is found to effective in reduce risk of hypertension and hyperlipidemia, why it does not contribute to the reduce risk of cerebral infarction (CI) and myocardial infarction in men with histories of hypertension and diabetes mellitus and medication use for hypercholesterolemia.
Would the medication is the cause? As epidemiological study insisted the lowering effect of blood pressure and cholesterol are associated to reduce risk heart disease and stroke.
b. Although soy isoflavone showed an effectiveness in reduce risk of cerebral infarction (CI) and myocardial infarction and mortality, would dietary with high in fruit and vegetable also best known for the reduce risk of heart disease and stroke be also taken into account?
c. The effectiveness of the study may only be true for equol producers population as 90% of subjects' study are equol producers?
b. Would the "Japanese Phenomenon" interfere with the study, as administration of isoflavone "inexperienced" women at the time of menopause, the phytoestrogens appear to share the same effects as estrogen used in classical preparations for hormone replacement therapy?
References
(a) The Science of Soy: What Do We Really Know? by Julia R. Barrett
(b) Guideline for healthy soy intake(the Unite Soybean board)
(1) Japan, Wikipedia
(1a) Erdman JW Jr. AHA Science Advisory: soy protein and cardiovascular disease: a statement for healthcare professionals from the Nutrition Committee of the AHA. Circulation. 2000; 102: 2555–2559
(Soy protein and cardiovascular disease)
(1b) van der Schouw YT, Kreijkamp-Kaspers S, Peeters PH, Keinan-Boker L, Rimm EB, Grobbee DE. Prospective study on usual dietary phytoestrogen intake and cardiovascular disease risk in Western women. Circulation. 2005; 111: 465–471(Cardiovascular diseases in women)
(5) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population by Nagata C1, Mizoue T, Tanaka K, Tsuji I, Tamakoshi A, Matsuo K, Wakai K, Inoue M, Tsugane S, Sasazuki S; Research Group for the Development and Evaluation of Cancer Prevention Strategies in Japan.(PubMed)
(6) Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study by Toi M1, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T, Tokuda Y, Masuda N, Ohsumi S, Ohno S, Takahashi M, Hayashi H, Yamamoto S, Ohashi Y.(PubMed)
(7) Associations of intakes of fat, dietary fiber, soy isoflavones, and alcohol with levels of sex hormones and prolactin in premenopausal Japanese women by Tsuji M1, Tamai Y, Wada K, Nakamura K, Hayashi M, Takeda N, Yasuda K, Nagata C.(PubMed)
(8) Plasma isoflavone level and subsequent risk of breast cancer among Japanese women: a nested case-control study from the Japan Public Health Center-based prospective study group by Iwasaki M1, Inoue M, Otani T, Sasazuki S, Kurahashi N, Miura T, Yamamoto S, Tsugane S; Japan Public Health Center-based prospective study group.(PubMed)
(9) Isoflavones--safe food additives or dangerous drugs? by Wuttke W1, Jarry H, Seidlová-Wuttke D.(PubMed)
(10) Effect of a soybean product on serum lipid levels in female university students by Takahashi K1, Kamada Y, Hiraoka-Yamamoto J, Mori M, Nagata R, Hashimoto K, Aizawa T, Matsuda K, Kometani T, Ikeda K, Yamori Y.(PubMed)
(11) Ecological study of the association between soy product intake and mortality from cancer and heart disease in Japan by Nagata C.(PubMed)
(12) Association of blood pressure with intake of soy products and other food groups in Japanese men and women by Nagata C1, Shimizu H, Takami R, Hayashi M, Takeda N, Yasuda K.(PubMed)
(14) Effects of dietary intake of soy protein and isoflavones on cardiovascular disease risk factors in high risk, middle-aged men in Scotland by Sagara M1, Kanda T, NJelekera M, Teramoto T, Armitage L, Birt N, Birt C, Yamori Y.(PubMed)
A.2. Soy and Breast cancer in Japanese women
Breast cancer (malignant breast neoplasm) is a cancer that starts in the tissues of the breast either from the inner lining of milk ducts (Ductal carcinoma) or the lobules (Lobular carcinoma) that supply the ducts with milk. there is also rare cases that breast cancer starts in other areas of the breast. In 2010, over 250,000 new cases of breast cancer were expected to be diagnosed in women in the U.S. alone and the risk of getting invasive breast cancer during life time of a women is 1/8.
The searching of keyword in PubMed with keywords, soy and breast cancer in Japanese women, found 15 related studies.
Epidemiologic evidence suggesting high intake of soy in Japanese population is associated to reduce risk of breast cancer(1) and regular consumption of probiotic beverage and isoflavones since adolescence was inversely associated with the incidence of breast cancer in Japanese women(2)(2a).
The study in the testing of oral administration of IF-rich tablet (20 and 40 mg/day) on climacteric women, showed the product not only reduced risk of breast cancer but also showed an improvement of bone density, hypertension and climacteric symptoms, cardiovascular diseases, gynecological problems and possible immune potentiation(3)
Japanese women show lower incidence of and mortality from breast cancer, compared to Caucasians, it may be result of large amount intake soy protein and isoflavones, as high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects(4).
According to the Loma Linda University, Asian population consumes as much as 25 g of soy protein or 100 mg of isoflavones per day(5).
Epidemiological Western studies have link levels of Genistein and daidzein in stimulating breast tumor growth and antagonize the effects of tamoxifen have been inclusive. Some researchers suggested that women with current or past breast cancer should be aware of the risks of potential tumor growth when taking soy products(6).
In Japanese population, serum of isoflavones and insulin levels were not associated with breast cancer risk, in a case-control study of 63 histologically confirmed breast cancer patients and 76 controls, of serum isoflavone, insulin and adiponectin levels with breast cancer risk(7).
The review of Soy for breast cancer survivors, also rejected the above claim of adult consumption of soy affects the risk of developing breast cancer or that soy consumption affects the survival of breast cancer patients(8). In deed, in Japanese study in testing the serum concentrations of genistein and daidzein, showed urinary excretion in 10 women and 9 men who consumed a typical low-fat diet with much rice and soy products, fish, and vegetables, in a rural village south of Kyoto, Japan, indicated a co-related to isoflavonoids intake and serum concentrations of genistein and daidzein and suggested that these may be a result of low mortality in breast and prostate cancer of Japanese women and men, respectively(9). In fact, tofu is found to be associated with the serum concentrations of genistein and daidzein but fermented product, such as miso showed a slight association with serum concentrations of these phytoestrogens with serum concentrations of equol showed associated with dietary intake of tofu and miso soup(10).
Soymilk, a flavor drink on breakfast in Asian diet, when conbined with combination with probiotic Lactobacillus casei Shirota (LcS) also showed to prevent the development of mammary tumors through suppressesion of tumor growth and might be a beneficial dietary style for breast cancer prevention(11). Intake of soy combined with seaweed in equol producers, showed seaweed favorably alters estrogen and phytoestrogen metabolism and these changes likely include modulation of colonic bacteria, in healthy postmenopausal women(12). In premenopausal Japanese women study with randomly assigned to receive either a soymilk-supplemented diet (n = 31) or a normal (control) diet (n = 29), involved three consecutive menstrual cycles showed the estrone and estradiol levels were decreased by 23% and 27%, respectively, in the soymilk-supplemented group but insisted that larger studies will be required to confirm the ability of soy products to reduce serum estrogen levels(12a). Other study in 50 healthy premenopausal Japanese women, also showed a similar result as blood samples drawn from each subject on Days 11 and 22 of her menstrual cycle, suggested that the consumption of soy products lowers the risk of developing breast cancer risk in modifying estrogen metabolism(12b).
In postmenopausal Japanese women, according to the study from the Takayama, with participants members aged 35 years or older in 1992 with follow-up was conducted from the time of the baseline study (September 1, 1992) to the end of March 2008, concluded that soy and isoflavone intakes may have a protective effect on postmenopausal breast cancer. Risks of breast cancer were decreased among women with a moderate intake of soy and isoflavone(13).
In a total of 678 breast cancer cases and 3,390 age- and menopausal status-matched noncancer controls, soy showed a protective effect against breast cancer risk differs by receptor status, including with ER-positive (ER+) and HER2-negative (HER2-)(14). Genistein a major component of soybean isoflavone, has been found to induce breast cancer in some Western study, also exert its anti breast cancer preventive effect in a breast cancer cell overexpressing HER-2, as genistein enhances necrotic-like cell death of the breast cancer cells through the inactivation of HER-2 receptor and Akt which plays a key role in multiple cellular processes in combined with chemotherapeutic agent (15).
Unfortunately, report on a Japan Collaborative Cohort (JACC) Study. From 1988 to 1990, 30,454 women aged 40-79 years, completed a questionnaire on diet and other lifestyle features, suggested that consumption of soy food has no protective effects against breast cancer, but insisted that further large-scale investigations eliciting genetic factors may clarify different roles of various soybean-ingredient foods on the risk of breast cancer(16).
According to DR. Nagata C. the protective risk against breast cancer only found in in Asian but not Western populations with intake of soy may be due to consume levels of soy typical in Asian diets. researchers should also take account of amount of soy isoflavones consumed, the form and food source of isoflavones, timing of isoflavone exposure, estrogen receptor status of tumors, and equol-producer status and hormonal profile of individuals. These factors might explain the heterogeneity of results from studies(17).
Conclusion
Dr, Rice S. Dr. Whitehead SA., in the differentiation of phytoestrogens and breast cancer--promoters or protectors? said "a paradox concerning the epidemiology of breast cancer and the dietary intake of phytoestrogens that bind weakly to oestrogen receptors and initiate oestrogen-dependent transcription. In Eastern countries, such as Japan, the incidence of breast cancer is approximately one-third that of Western countries whilst their high dietary intake of phytoestrogens, mainly in the form of soy products, can produce circulating levels of phytoestrogens that are known experimentally to have oestrogenic effects. The actions of phytoestrogens on oestrogen receptors and key enzymes that convert androgens to oestrogens in relation to the growth of breast cancer cells. In addition, it compares the experimental and epidemiological evidence pertinent to the potential beneficial or harmful effects of phytoestrogens in relation to the incidence/progression of breast cancer and their efficacy as natural alternatives to conventional HRT"(18).
References
(1) Soy intake and breast cancer risk: an evaluation based on a systematic review of epidemiologic evidence among the Japanese population(PubMed)
(2) Probiotic Beverage with Soy Isoflavone Consumption for Breast Cancer Prevention: A Case-control Study by Toi M1, Hirota S, Tomotaki A, Sato N, Hozumi Y, Anan K, Nagashima T, Tokuda Y, Masuda N, Ohsumi S, Ohno S, Takahashi M, Hayashi H, Yamamoto S, Ohashi Y.(PubMed)
(2a) Yamamoto S1, Sobue T, Kobayashi M, Sasaki S, Tsugane S; Japan Public Health Center-Based Prospective Study on Cancer Cardiovascular Diseases Group.(PubMed)
(3) Isoflavones for prevention of cancer, cardiovascular diseases, gynecological problems and possible immune potentiation by Watanabe S1, Uesugi S, Kikuchi Y.(PubMed)
(4) Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)
(5) Estimated Asian adult soy protein and isoflavone intakes, by Messina M1, Nagata C, Wu AH.(PubMed).
(6) Effects of soy phytoestrogens genistein and daidzein on breast cancer growth by de Lemos ML.(PubMed)
(7) Minatoya M1, Kutomi G, Asakura S, Otokozawa S, Sugiyama Y, Ohnishi H, Akasaka H, Miura T, Mori M, Hirata K.(PubMed)
(8) Soy for breast cancer survivors: a critical review of the literature by Messina MJ1, Loprinzi CL.(PubMed)
(9) Association of serum phytoestrogen concentration and dietary habits in a sample set of the JACC Study by Ozasa K1, Nakao M, Watanabe Y, Hayashi K, Miki T, Mikami K, Mori M, Sakauchi F, Washio M, Ito Y, Suzuki K, Kubo T, Wakai K, Tamakoshi A; JACC Study Group.(PubMed)
(10) Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet by Adlercreutz H1, Honjo H, Higashi A, Fotsis T, Hämäläinen E, Hasegawa T, Okada H.(PubMed)
(11) Lactobacillus casei Shirota enhances the preventive efficacy of soymilk in chemically induced breast cancer by Kaga C1, Takagi A, Kano M, Kado S, Kato I, Sakai M, Miyazaki K, Nanno M, Ishikawa F, Ohashi Y, Toi M.(PubMed)
(12) Dietary seaweed modifies estrogen and phytoestrogen metabolism in healthy postmenopausal women by Teas J1, Hurley TG, Hebert JR, Franke AA, Sepkovic DW, Kurzer MS.(PubMed)
(12a) Effect of soymilk consumption on serum estrogen concentrations in premenopausal Japanese women by Nagata C1, Takatsuka N, Inaba S, Kawakami N, Shimizu H.(PubMed)
(12b) Decreased serum estradiol concentration associated with high dietary intake of soy products in premenopausal Japanese women by Nagata C1, Kabuto M, Kurisu Y, Shimizu H.(PubMed)
(13) Soy isoflavone intake and breast cancer risk in Japan: from the Takayama study by Wada K1, Nakamura K, Tamai Y, Tsuji M, Kawachi T, Hori A, Takeyama N, Tanabashi S, Matsushita S, Tokimitsu N, Nagata C.(PubMed)
(14) Effect of soybean on breast cancer according to receptor status: a case-control study in Japan by Suzuki T1, Matsuo K, Tsunoda N, Hirose K, Hiraki A, Kawase T, Yamashita T, Iwata H, Tanaka H, Tajima K.(PubMed)
(15) Genistein, a soy isoflavone, enhances necrotic-like cell death in a breast cancer cell treated with a chemotherapeutic agent by Satoh H1, Nishikawa K, Suzuki K, Asano R, Virgona N, Ichikawa T, Hagiwara K, Yano T.(PubMed)
(16) Consumption of soy foods and the risk of breast cancer: findings from the Japan Collaborative Cohort (JACC) Study by Nishio K1, Niwa Y, Toyoshima H, Tamakoshi K, Kondo T, Yatsuya H, Yamamoto A, Suzuki S, Tokudome S, Lin Y, Wakai K, Hamajima N, Tamakoshi A(PubMed)
(17) Factors to consider in the association between soy isoflavone intake and breast cancer risk.
PubMed)
(18) Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)
A3. Soy and Prostate cancer in Japanese Men
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.
The widespread of prostate cancer, once considered a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to effect even younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades.
In fact, the incidence of prostate cancer is still lower if compared to their Western counterparts.
The study of the Research Center for Cancer Prevention and Screening, National Cancer Center. suggested that isoflavones and soy food are associated with a dose-dependent decrease in the risk of localized cancer, in a population-based prospective study in 43,509 Japanese men ages 45 to 74 years with participants responded to a validated questionnaire, which included 147 food items. During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage(5).
Environment, Diet, intestinal microbiota and Geography
The testing of North American Japanese and Japanese in Japan showed the environment factor may be involved in the development of prostate cancer regardless to genetic similar(7). The incidence of the disease increased vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men(2).
The study of the associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men, showed that soy isoflavone significantly decreased the risk of prostate cancer regardless to the intake of other nutrients such as PUFA, (n-6) fatty acids or magnesium from other food sources(9).
Other suggested that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer(10).
DR. Akaza H. said "not having equol converting bacteria in the intestine (non-equol producers) can be a risk factor for prostate cancer and that one direction for future research will be to examine the possibility of improving the intestinal environment to enable equol production"(13).
Genes differentiation
1n gene differentiation, estrogen related genes may be the culprits for the development of prostate cancer. In an one hundred and eighty cases and 177 controls selected from three geographic areas of Japan study, though analysis by the multifactor dimensionality reduction method, soy isoflavones, showed to exhibit its anti prostate cancer, depending to differ between the genotypes of estrogen related genes(3).
According to Dr. Kimura T., the incidence of prostate cancer in Asia is much lower than that in African Americans and European Caucasians and soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer, it may be as a result of genetic mutation of approximately 30 genetic polymorphisms in populations of countries in the West.(1).
Serum of isoflavones
In a case-control study within the Japan Public Health Center-based Prospective of a total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples observed from 1990 to 2005, showed that plazma genistein level is associated inversely to the risk of prostate cancer(4).
Other in the study of four isoflavonoids in plasma of 14 Japanese and 14 Finnish men, also showed that the mean plasma of total individual isoflavonoid levels of Japnaese are 7 to 110 times higher Japanese than in the Finnish men. Genistein, a tyrosine kinase inhibitor, occurred in the highest concentration(11).
In the experiment of Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet showed that the excretion of isoflavonoids correlated with soybean-product intake is associated to reduced mortality in breast and prostate cancer of Japanese women and men(12).
In view of above, the Loma Linda University, insisted that soy isoflavones should be tested against different populations of prostate cancer patients for its efficacy(6). Other suggested that the lower incidence of prostate cancer in Japanese men may be a result of traditional Japanese diet with a lot of soy foods and fishes(8). Together with Soy-derived food products and the metabolization of the isoflavones they contain by intestinal microbiota among Asian and European/North American populations(13).
Natural Remedies for Dementia Memory Loss ReversalGuarantee to Stop Progression and Reverse Memory Loss in Alzheimer and Dementia with step by step instructions through Scientific Studies within 2 Months or your Money back
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians by Kimura T.(PubMed)
(2) Hereditary prostate cancer and other genetic predispositions to prostate cancer by Cussenot O1, Valeri A, Berthon P, Fournier G, Mangin P.(PubMed)
(3) Polymorphisms in estrogen related genes may modify the protective effect of isoflavones against prostate cancer risk in Japanese men by Sonoda T1, Suzuki H, Mori M, Tsukamoto T, Yokomizo A, Naito S, Fujimoto K, Hirao Y, Miyanaga N, Akaza H.(PubMed)
(4) Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center by Kurahashi N1, Iwasaki M, Inoue M, Sasazuki S, Tsugane S.(PubMed)
(5) Soy product and isoflavone consumption in relation to prostate cancer in Japanese men by Kurahashi N1, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S; Japan Public Health Center-Based Prospective Study Group.(PubMed)
(6) An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels by Messina M1, Kucuk O, Lampe JW.(PubMed)
(7) Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue by Marks LS1, Kojima M, Demarzo A, Heber D, Bostwick DG, Qian J, Dorey FJ, Veltri RW, Mohler JL, Partin AW.(PubMed)
(8) A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet by Sonoda T1, Nagata Y, Mori M, Miyanaga N, Takashima N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Fujioka T, Akaza H.(PubMed)
(9) Nagata Y1, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Akaza H.(PubMed)
(10) Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study by Kolonel LN1, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW, Paffenbarger RS Jr.(PubMed)
(11) Plasma concentrations of phyto-oestrogens in Japanese men by Adlercreutz H1, Markkanen H, Watanabe S.(PubMed)
(18) Phytoestrogens and breast cancer--promoters or protectors? by Rice S1, Whitehead SA.(PubMed)
A3. Soy and Prostate cancer in Japanese Men
Prostate cancer is defined as a condition in which the cells of prostate has become cancerous, causing abnormal cell growth with possibility of spreading to the distant parts of the body. Most prostate cancers are slow growing and enlarged prostate and prostate cancer may be detected during physical (rectum) exams.
The widespread of prostate cancer, once considered a disease of aging male, now have become major concerns of governments and scientific community in South East Asian with tendency to effect even younger age population. Suggestions emerged of over consuming bad fats in any time in history accompanied with unhealthy diet and life style may be the possible causes of the disease, linking to the economic prosperity over 2 decades.
In fact, the incidence of prostate cancer is still lower if compared to their Western counterparts.
The study of the Research Center for Cancer Prevention and Screening, National Cancer Center. suggested that isoflavones and soy food are associated with a dose-dependent decrease in the risk of localized cancer, in a population-based prospective study in 43,509 Japanese men ages 45 to 74 years with participants responded to a validated questionnaire, which included 147 food items. During follow-up from 1995 through 2004, 307 men were newly diagnosed with prostate cancer, of which 74 cases were advanced, 220 cases were organ localized, and 13 cases were of an undetermined stage(5).
Environment, Diet, intestinal microbiota and Geography
The testing of North American Japanese and Japanese in Japan showed the environment factor may be involved in the development of prostate cancer regardless to genetic similar(7). The incidence of the disease increased vary both from country to country and according to the ethnic group, with the highest incidence reported for Afro-Americans and the lowest for Asian men(2).
The study of the associations between nutritional and other lifestyle factors and the prevalence of prostate cancer in a case-control study of Japanese men, showed that soy isoflavone significantly decreased the risk of prostate cancer regardless to the intake of other nutrients such as PUFA, (n-6) fatty acids or magnesium from other food sources(9).
Other suggested that legumes (not limited to soy products) and certain categories of vegetables may protect against prostate cancer(10).
DR. Akaza H. said "not having equol converting bacteria in the intestine (non-equol producers) can be a risk factor for prostate cancer and that one direction for future research will be to examine the possibility of improving the intestinal environment to enable equol production"(13).
Genes differentiation
1n gene differentiation, estrogen related genes may be the culprits for the development of prostate cancer. In an one hundred and eighty cases and 177 controls selected from three geographic areas of Japan study, though analysis by the multifactor dimensionality reduction method, soy isoflavones, showed to exhibit its anti prostate cancer, depending to differ between the genotypes of estrogen related genes(3).
According to Dr. Kimura T., the incidence of prostate cancer in Asia is much lower than that in African Americans and European Caucasians and soy food consumption, more popular in Asian populations, is associated with a 25% to 30% reduced risk of prostate cancer, it may be as a result of genetic mutation of approximately 30 genetic polymorphisms in populations of countries in the West.(1).
Serum of isoflavones
In a case-control study within the Japan Public Health Center-based Prospective of a total of 14,203 men aged 40 to 69 years who had returned the baseline questionnaire and provided blood samples observed from 1990 to 2005, showed that plazma genistein level is associated inversely to the risk of prostate cancer(4).
Other in the study of four isoflavonoids in plasma of 14 Japanese and 14 Finnish men, also showed that the mean plasma of total individual isoflavonoid levels of Japnaese are 7 to 110 times higher Japanese than in the Finnish men. Genistein, a tyrosine kinase inhibitor, occurred in the highest concentration(11).
In the experiment of Urinary excretion of lignans and isoflavonoid phytoestrogens in Japanese men and women consuming a traditional Japanese diet showed that the excretion of isoflavonoids correlated with soybean-product intake is associated to reduced mortality in breast and prostate cancer of Japanese women and men(12).
In view of above, the Loma Linda University, insisted that soy isoflavones should be tested against different populations of prostate cancer patients for its efficacy(6). Other suggested that the lower incidence of prostate cancer in Japanese men may be a result of traditional Japanese diet with a lot of soy foods and fishes(8). Together with Soy-derived food products and the metabolization of the isoflavones they contain by intestinal microbiota among Asian and European/North American populations(13).
Natural Remedies for Dementia Memory Loss ReversalGuarantee to Stop Progression and Reverse Memory Loss in Alzheimer and Dementia with step by step instructions through Scientific Studies within 2 Months or your Money back
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) East meets West: ethnic differences in prostate cancer epidemiology between East Asians and Caucasians by Kimura T.(PubMed)
(2) Hereditary prostate cancer and other genetic predispositions to prostate cancer by Cussenot O1, Valeri A, Berthon P, Fournier G, Mangin P.(PubMed)
(3) Polymorphisms in estrogen related genes may modify the protective effect of isoflavones against prostate cancer risk in Japanese men by Sonoda T1, Suzuki H, Mori M, Tsukamoto T, Yokomizo A, Naito S, Fujimoto K, Hirao Y, Miyanaga N, Akaza H.(PubMed)
(4) Plasma isoflavones and subsequent risk of prostate cancer in a nested case-control study: the Japan Public Health Center by Kurahashi N1, Iwasaki M, Inoue M, Sasazuki S, Tsugane S.(PubMed)
(5) Soy product and isoflavone consumption in relation to prostate cancer in Japanese men by Kurahashi N1, Iwasaki M, Sasazuki S, Otani T, Inoue M, Tsugane S; Japan Public Health Center-Based Prospective Study Group.(PubMed)
(6) An overview of the health effects of isoflavones with an emphasis on prostate cancer risk and prostate-specific antigen levels by Messina M1, Kucuk O, Lampe JW.(PubMed)
(7) Prostate cancer in native Japanese and Japanese-American men: effects of dietary differences on prostatic tissue by Marks LS1, Kojima M, Demarzo A, Heber D, Bostwick DG, Qian J, Dorey FJ, Veltri RW, Mohler JL, Partin AW.(PubMed)
(8) A case-control study of diet and prostate cancer in Japan: possible protective effect of traditional Japanese diet by Sonoda T1, Nagata Y, Mori M, Miyanaga N, Takashima N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Fujioka T, Akaza H.(PubMed)
(9) Nagata Y1, Sonoda T, Mori M, Miyanaga N, Okumura K, Goto K, Naito S, Fujimoto K, Hirao Y, Takahashi A, Tsukamoto T, Akaza H.(PubMed)
(10) Vegetables, fruits, legumes and prostate cancer: a multiethnic case-control study by Kolonel LN1, Hankin JH, Whittemore AS, Wu AH, Gallagher RP, Wilkens LR, John EM, Howe GR, Dreon DM, West DW, Paffenbarger RS Jr.(PubMed)
(11) Plasma concentrations of phyto-oestrogens in Japanese men by Adlercreutz H1, Markkanen H, Watanabe S.(PubMed)
(13) Prostate cancer chemoprevention by soy isoflavones: role of intestinal bacteria as the "second human genome" by Akaza H.(PubMed)
Thursday, May 22, 2014
Herbal Angelica and Diabetes
Dang Qui (Angelica root) may be used alone and conjunction with other herbs in reduced blood glucose of patient with diabetes new study suggested.
According to the 2011 statistic from National Diabetes InformationClearinghouse (NDIC), among U.S. residents ages 65 years and older, 10.9 million, or 26.9 percent, had diabetes in 2010, about 215,000 people younger than 20 years had diabetes—type 1 or type 2—in the United States in 2010 and approximately, 1.9 million people ages 20 years or older were newly diagnosed with diabetes in 2010 in the United States.
Beside acting as a queen herb in balancing the hormones in women for a normal menstrual cycle and menstruation, Dang Qui also used in traditional Chinese medicine to treat gynecological ailments, fatigue, mild anemia and high blood pressure. It has analgesic, anti-inflammatory, etc.(1)
Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis of Chinese herbal fomula, showed to significantly alleviate the hyperglycemia but made no influence on plasma lipid profiles nor weight gain in fructose chow-fed rats when applied alone, through through increased post-receptor insulin signaling(2). Together with Panax notoginseng (RRP), the extract showed to reverse high glucose-induced inhibition of endothelial cell migration and proliferation, through decreased the expression of inflammatory factors(3).
Decursin, an active compound isolated from Angelica gigas, showed a significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1 associated to diabetes and obesity(4)
Angelica Keiskei, another member of Angelica improved insulin resistance in diabetes of rats induced by streptozotocin with intraperitoeal injection as well as with high-fat diet feeding through upregulation of the mRNA expression levels of PI3K and Akt(5).
Dr, Zhao Y. and the research team at the Medical College of Qingdao University aslo in the study of the effect of Angelica Keiskei in diabetes told PubMed " Angelica keiskei chalcone (the extract) may increase the expression levels of Glut2 in liver and Glut4 in skeletal muscle cells, decrease fasting blood glucose and insulin of type 2 diabetic rats and improve their insulin resistance condition"(6).
Unfortunately, oral administration of angelica have linked to proliferation of the breast cancer for women with history of breast cancer and gene mutation Her-2(7)(8).
Taken altogether, Dang Qui may be effective in reduced glucose level of patients with type II diabetes and can be considered for prevention of diabetic complications. Due to its conflict results in breast cancer studies, it is advice that women with mutation gene Her or with history of breast cancer should consult their Doctor & Related field specialist before applying. As always, all articles written by Kyle J. Norton are for information & education only,
Natural Remedies for Dementia Memory Loss ReversalGuarantee to Stop Progression and Reverse Memory Loss in Alzheimer and Dementia with step by step instructions through Scientific Studies within 2 Months or your Money back
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) Popular #Herbs - #Dang Qui (Angelica sinensis)
(2) A Chinese Herbal Decoction, Dang Gui Bu Xue Tang, Prepared from Radix Astragali and Radix Angelicae sinensis, Ameliorates Insulin Resistance Induced by A High-Fructose Diet in Rats by Liu IM1, Tzeng TF, Liou SS(PubMed)
(3) An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy by Gao D1, Guo Y, Li X, Li X, Li Z, Xue M, Ou Z, Liu M, Yang M, Liu S, Yang S.(PubMed)
(4) [Effect of ashitabe chalcones on the mRNA expression of PI3K and Akt in hepatocytes of rats with diabetes].[Article in Chinese] by Liu B1, Sun J, Zhao Y, Li L, Zhong J.(PubMed)
(5) Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet by Hwang JT1, Kim SH, Hur HJ, Kim HJ, Park JH, Sung MJ, Yang HJ, Ryu SY, Kim YS, Cha MR, Kim MS, Kwon DY.(PubMed)
(6) [Effects of angelica keiskei chalcone on expression of glucose transporter proteins in liver and skeletal muscle cells of type 2 diabetic rats].[Article in Chinese] by Zhao Y1, Liu B, Li L, Zhong J.(PubMed)
(7) Use of dong quai (Angelica sinensis) to treat peri- or postmenopausal symptoms in women with breast cancer: is it appropriate? by Lau CB1, Ho TC, Chan TW, Kim SC.(PubMed)
(8) Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells by Chang CJ1, Chiu JH, Tseng LM, Chang CH, Chien TM, Wu CW, Lui WY.(PubMed)
According to the 2011 statistic from National Diabetes InformationClearinghouse (NDIC), among U.S. residents ages 65 years and older, 10.9 million, or 26.9 percent, had diabetes in 2010, about 215,000 people younger than 20 years had diabetes—type 1 or type 2—in the United States in 2010 and approximately, 1.9 million people ages 20 years or older were newly diagnosed with diabetes in 2010 in the United States.
Beside acting as a queen herb in balancing the hormones in women for a normal menstrual cycle and menstruation, Dang Qui also used in traditional Chinese medicine to treat gynecological ailments, fatigue, mild anemia and high blood pressure. It has analgesic, anti-inflammatory, etc.(1)
Dang Gui Bu Xue Tang (DBT), an aqueous extract of Radix Astragali and Radix Angelica sinensis of Chinese herbal fomula, showed to significantly alleviate the hyperglycemia but made no influence on plasma lipid profiles nor weight gain in fructose chow-fed rats when applied alone, through through increased post-receptor insulin signaling(2). Together with Panax notoginseng (RRP), the extract showed to reverse high glucose-induced inhibition of endothelial cell migration and proliferation, through decreased the expression of inflammatory factors(3).
Decursin, an active compound isolated from Angelica gigas, showed a significantly reduced the secretion of HFD-induced adipocytokines such as leptin, resistin, IL-6 and MCP-1 associated to diabetes and obesity(4)
Angelica Keiskei, another member of Angelica improved insulin resistance in diabetes of rats induced by streptozotocin with intraperitoeal injection as well as with high-fat diet feeding through upregulation of the mRNA expression levels of PI3K and Akt(5).
Dr, Zhao Y. and the research team at the Medical College of Qingdao University aslo in the study of the effect of Angelica Keiskei in diabetes told PubMed " Angelica keiskei chalcone (the extract) may increase the expression levels of Glut2 in liver and Glut4 in skeletal muscle cells, decrease fasting blood glucose and insulin of type 2 diabetic rats and improve their insulin resistance condition"(6).
Unfortunately, oral administration of angelica have linked to proliferation of the breast cancer for women with history of breast cancer and gene mutation Her-2(7)(8).
Taken altogether, Dang Qui may be effective in reduced glucose level of patients with type II diabetes and can be considered for prevention of diabetic complications. Due to its conflict results in breast cancer studies, it is advice that women with mutation gene Her or with history of breast cancer should consult their Doctor & Related field specialist before applying. As always, all articles written by Kyle J. Norton are for information & education only,
Natural Remedies for Dementia Memory Loss ReversalGuarantee to Stop Progression and Reverse Memory Loss in Alzheimer and Dementia with step by step instructions through Scientific Studies within 2 Months or your Money back
Super foods Library, Eat Yourself Healthy With The Best of the Best Nature Has to Offer
For over 100 healthy recipes, http://diseases-researches.blogspot.ca/p/blog-page_17.html
References
(1) Popular #Herbs - #Dang Qui (Angelica sinensis)
(2) A Chinese Herbal Decoction, Dang Gui Bu Xue Tang, Prepared from Radix Astragali and Radix Angelicae sinensis, Ameliorates Insulin Resistance Induced by A High-Fructose Diet in Rats by Liu IM1, Tzeng TF, Liou SS(PubMed)
(3) An Aqueous Extract of Radix Astragali, Angelica sinensis, and Panax notoginseng Is Effective in Preventing Diabetic Retinopathy by Gao D1, Guo Y, Li X, Li X, Li Z, Xue M, Ou Z, Liu M, Yang M, Liu S, Yang S.(PubMed)
(4) [Effect of ashitabe chalcones on the mRNA expression of PI3K and Akt in hepatocytes of rats with diabetes].[Article in Chinese] by Liu B1, Sun J, Zhao Y, Li L, Zhong J.(PubMed)
(5) Decursin, an active compound isolated from Angelica gigas, inhibits fat accumulation, reduces adipocytokine secretion and improves glucose tolerance in mice fed a high-fat diet by Hwang JT1, Kim SH, Hur HJ, Kim HJ, Park JH, Sung MJ, Yang HJ, Ryu SY, Kim YS, Cha MR, Kim MS, Kwon DY.(PubMed)
(6) [Effects of angelica keiskei chalcone on expression of glucose transporter proteins in liver and skeletal muscle cells of type 2 diabetic rats].[Article in Chinese] by Zhao Y1, Liu B, Li L, Zhong J.(PubMed)
(7) Use of dong quai (Angelica sinensis) to treat peri- or postmenopausal symptoms in women with breast cancer: is it appropriate? by Lau CB1, Ho TC, Chan TW, Kim SC.(PubMed)
(8) Modulation of HER2 expression by ferulic acid on human breast cancer MCF7 cells by Chang CJ1, Chiu JH, Tseng LM, Chang CH, Chien TM, Wu CW, Lui WY.(PubMed)
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